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Mo X, Men Z, Gao L, Gao Y, Yao T, Liu Y, Yuan Y, Xue T, Wang F, Wang S, Wang K, Liang X, Feng Y. Immunogenicity persistence after four intramuscular triple-dose or standard-dose hepatitis B vaccine in patients receiving methadone maintenance treatment: A 1-year follow-up study in China. Hum Vaccin Immunother 2025; 21:2447108. [PMID: 39819251 DOI: 10.1080/21645515.2024.2447108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 12/09/2024] [Accepted: 12/22/2024] [Indexed: 01/19/2025] Open
Abstract
CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (NCT03962816).https://clinicaltrials.gov/ct2/show/NCT03962816.
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Affiliation(s)
- Xinyuan Mo
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University) Ministry of Education, Taiyuan, Shanxi, China
| | - Zhaoyue Men
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University) Ministry of Education, Taiyuan, Shanxi, China
| | - Linying Gao
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yizhuo Gao
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Tian Yao
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
- First Hospital/First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Yuan Liu
- Methadone Maintenance Treatment Clinic, Compulsory Isolation Drug Rehabilitation Center, Taiyuan, Shanxi, China
| | - Yuan Yuan
- Methadone Maintenance Treatment Clinic, 109 hospital, Taiyuan, Shanxi, China
| | - Tongchuan Xue
- Xinghualing District Methadone Maintenance Treatment Clinic, Taiyuan, Shanxi, China
| | - Fuzhen Wang
- Chinese Center for Disease Control and Prevention, Beijing, China
| | - Suping Wang
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University) Ministry of Education, Taiyuan, Shanxi, China
| | - Keke Wang
- First Hospital/First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China
| | - Xiaofeng Liang
- Institute of Vaccine Industry, Institute of Disease Control and Prevention, Jinan University, Guangzhou, Guangdong, China
- Chinese Preventive Medicine Association, Beijing, China
| | - Yongliang Feng
- School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, Shanxi, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University) Ministry of Education, Taiyuan, Shanxi, China
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Zięba K, Jagiełło K, Musialik J, Wierucki Ł, Hajduk A, Mossakowska M, Chudek J. Anti-HBs Positivity Related to Past HBV Infection and Vaccination in Older Adults in Polish Population-Cohort-Based Study. Vaccines (Basel) 2024; 13:18. [PMID: 39852797 PMCID: PMC11768802 DOI: 10.3390/vaccines13010018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 12/21/2024] [Accepted: 12/24/2024] [Indexed: 01/26/2025] Open
Abstract
BACKGROUND In Poland, a national hepatitis B (HBV) immunization program was introduced for neonates in 1996, and between 2000 and 2011, those born from 1986 to 1995 were vaccinated. Little is known about vaccination rates among adults born before 1986. This study aimed to determine the frequency of anti-HBs seropositivity rates related to vaccination and past HBV infection in older Poles. METHODS The HBV serological status was analyzed in 5781 (96.6%) of the PolSenior2 population-based cohort (60+) by assessing serum seropositivity for HBs antigen, anti-HBs, and anti-HBc antibodies. The survey was performed in 2018-2019 and included medical and socio-economic questionnaires, anthropometric measurements, and comprehensive geriatric assessment. RESULTS Serological status implying past hepatitis B and serological profile consistent with anti-HBV vaccination corresponded to 15.2% (95% CI: 13.4-17.0) and 25.2% (95% CI: 23.4-27.0) prevalences, respectively. Female gender, living in a town or city, having better education, and suffering from coronary artery disease, or depression independently increased the rate of past hepatitis B. On the other hand, being 'white collar' and self-reliant, having the ability to use the Internet, and past surgical procedures in the last 5-year period were factors associated with a higher vaccination rate. CONCLUSIONS More than 15% of older adults in Poland present serological profiles suggesting past hepatitis B, and one-fourth anti-HBV vaccination. Being functionally independent, 'white collar', using the Internet, and having past surgical procedures are factors associated with a higher chance of being vaccinated. Nevertheless, a large group of older adults should be prophylactically vaccinated due to increased exposure to medical procedures.
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Affiliation(s)
- Katarzyna Zięba
- Department of Internal Medicine and Oncological Chemotherapy, Medical University of Silesia in Katowice, 40-029 Katowice, Poland;
| | - Kacper Jagiełło
- Department of Preventive Medicine and Education, Medical University of Gdańsk, 80-211 Gdańsk, Poland; (K.J.); (Ł.W.)
| | - Joanna Musialik
- Department of Nephrology, Transplantology and Internal Medicine, Medical University of Silesia in Katowice, 40-055 40-027 Katowice, Poland;
| | - Łukasz Wierucki
- Department of Preventive Medicine and Education, Medical University of Gdańsk, 80-211 Gdańsk, Poland; (K.J.); (Ł.W.)
| | - Adam Hajduk
- Department of Rheumatology, Clinical Immunology, Geriatrics and Internal Medicine, Medical University of Gdańsk, 80-214 Gdańsk, Poland;
| | - Małgorzata Mossakowska
- Study on Ageing and Longevity, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland;
| | - Jerzy Chudek
- Department of Internal Medicine and Oncological Chemotherapy, Medical University of Silesia in Katowice, 40-029 Katowice, Poland;
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Heisig J, Nurmatov ZS, Riese P, Trittel S, Sattarova GJ, Temirbekova SN, Zhumagulova GZ, Nuridinova ZN, Derkenbaeva AA, Arykbaeva BK, Dzhangaziev BI, Prokein J, Klopp N, Illig T, Guzmán CA, Kasymov OT, Akmatov MK, Pessler F. Vaccination Schedule and Age Influence Impaired Responsiveness to Hepatitis B Vaccination: A Randomized Trial in Central Asia. Pathogens 2024; 13:1082. [PMID: 39770341 PMCID: PMC11728755 DOI: 10.3390/pathogens13121082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 12/03/2024] [Accepted: 12/05/2024] [Indexed: 01/16/2025] Open
Abstract
Vaccination against hepatitis B virus (HBV) is the most cost-efficient measure to prevent infection. Still, vaccination coverage among adults in Central Asia, including Kyrgyzstan, remains suboptimal, and data about immune responses to HBV vaccination are lacking. HBV vaccination is given as three injections, whereby the second and third doses are given 1 and 6 months after the first (0-1-6 scheme). However, compliance with the third dose is low in Kyrgyzstan, presumably due to the long time interval between the second and third doses, suggesting that a shortened vaccination schedule could result in better adherence and increased seroconversion. Thus, we conducted a randomized trial of individuals aged 17-66 years comparing the 0-1-6 scheme against a shorter 0-1-3 scheme. Primary outcome measures were post-vaccination titers and the percentage of participants with protective post-vaccination titers (≥10 mIU/mL). Compliance with the completeness of blood draws and administered third vaccine dose was better with the 0-1-3 scheme than with the 0-1-6 scheme. In both study arms combined, younger age (<40 years) was associated with better vaccine protection. The 0-1-6 scheme resulted in higher post-vaccination titers (52 versus 15 mIU/mL, p = 0.002) and a higher seroprotection rate (85% versus 64%, p = 0.01) than the 0-1-3 scheme, whereby post-vaccination titers correlated negatively with age in the 0-1-3 scheme. Thus, the 0-1-6 scheme should continue to be the preferred HBV vaccination schedule, but interventions to improve compliance with the third vaccine dose are needed.
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Affiliation(s)
- Janyn Heisig
- Department Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; (J.H.); (P.R.); (S.T.); (C.A.G.)
| | - Zuridin Sh. Nurmatov
- National Institute of Public Health, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan; (Z.S.N.); (G.J.S.); (S.N.T.); (Z.N.N.); (A.A.D.)
| | - Peggy Riese
- Department Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; (J.H.); (P.R.); (S.T.); (C.A.G.)
| | - Stephanie Trittel
- Department Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; (J.H.); (P.R.); (S.T.); (C.A.G.)
| | - Gulsunai J. Sattarova
- National Institute of Public Health, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan; (Z.S.N.); (G.J.S.); (S.N.T.); (Z.N.N.); (A.A.D.)
| | - Saikal N. Temirbekova
- National Institute of Public Health, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan; (Z.S.N.); (G.J.S.); (S.N.T.); (Z.N.N.); (A.A.D.)
| | - Gulnara Zh. Zhumagulova
- Republican Center for Immunoprophylaxis, Ministry of Health of the Kyrgyz Republic, Bishkek 720040, Kyrgyzstan;
| | - Zhanylai N. Nuridinova
- National Institute of Public Health, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan; (Z.S.N.); (G.J.S.); (S.N.T.); (Z.N.N.); (A.A.D.)
| | - Aisuluu A. Derkenbaeva
- National Institute of Public Health, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan; (Z.S.N.); (G.J.S.); (S.N.T.); (Z.N.N.); (A.A.D.)
| | - Bubuzhan K. Arykbaeva
- Ministry of Health of the Kyrgyz Republic, Bishkek 720040, Kyrgyzstan; (B.K.A.); (B.I.D.)
| | - Bakyt I. Dzhangaziev
- Ministry of Health of the Kyrgyz Republic, Bishkek 720040, Kyrgyzstan; (B.K.A.); (B.I.D.)
| | - Jana Prokein
- Hannover Unified Biobank, Hannover Medical School, 30625 Hannover, Germany; (J.P.); (N.K.); (T.I.)
| | - Norman Klopp
- Hannover Unified Biobank, Hannover Medical School, 30625 Hannover, Germany; (J.P.); (N.K.); (T.I.)
| | - Thomas Illig
- Hannover Unified Biobank, Hannover Medical School, 30625 Hannover, Germany; (J.P.); (N.K.); (T.I.)
| | - Carlos A. Guzmán
- Department Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; (J.H.); (P.R.); (S.T.); (C.A.G.)
| | - Omor T. Kasymov
- Scientific and Production Centre for Preventive Medicine, Ministry of Health of the Kyrgyz Republic, Bishkek 720005, Kyrgyzstan;
| | - Manas K. Akmatov
- Research Group Biomarkers for Infectious Diseases, TWINCORE Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany;
| | - Frank Pessler
- Research Group Biomarkers for Infectious Diseases, TWINCORE Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany;
- Centre for Individualised Infection Medicine, 30625 Hannover, Germany
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Qiu Q, Wang H, Liu X, Pang X, Zhang W. Comparative Immunogenicity of a High-Dose Hepatitis B Virus (HBV) Vaccine with Rapid Immunization vs. Standard Schedule in HBV Vaccine-Naïve Adults Aged 25-55 in China. Vaccines (Basel) 2024; 12:923. [PMID: 39204046 PMCID: PMC11359784 DOI: 10.3390/vaccines12080923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 08/15/2024] [Accepted: 08/16/2024] [Indexed: 09/03/2024] Open
Abstract
The 20 μg (0-1-6 month) hepatitis B virus (HBV) vaccination is widely recommended for HBV vaccine-naïve immune adults in China. However, suboptimal protective responses may occur due to dose-series incompletion. We aim to investigate the immunogenicity of a 60 μg HB vaccine with a 0-2 month series among HBV vaccine-naïve immune adults aged 25-55 to assess potential alternative approaches for HB immunization. A two-center randomized controlled trial was carried out. Participants were randomly allocated to either the 20 μg (0-1-6 month) or the 60 μg (0-2 month) regimen. Blood samples were collected eight weeks after the final injection to measure the antibodies. A total of 583 adults (289 in the 20 μg regimen and 294 in the 60 μg regimen) were included. The seroprotection rates (SPRs) were 97.23% and 93.54% in the 20 μg and 60 μg regimens, respectively (p = 0.0261), and the geometric mean concentrations were 600.76 mIU/mL and 265.68 mIU/mL, respectively (p < 0.0001). The immunogenicity of the 60 μg regimen decreased significantly with age, particularly in adults aged 40 and older. The 60 μg regimen may be beneficial for adults under 40, especially those with poor compliance or in urgent need of immunization.
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Affiliation(s)
| | | | | | | | - Wei Zhang
- Beijing Center for Disease Prevention and Control, Beijing 100013, China; (Q.Q.)
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Bello N, Hudu SA, Alshrari AS, Imam MU, Jimoh AO. Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review. Pathogens 2024; 13:554. [PMID: 39057781 PMCID: PMC11279426 DOI: 10.3390/pathogens13070554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND The advent of the hepatitis B vaccine has achieved tremendous success in eradicating and reducing the burden of hepatitis B infection, which is the main culprit for hepatocellular carcinoma-one of the most fatal malignancies globally. Response to the vaccine is achieved in about 90-95% of healthy individuals and up to only 50% in immunocompromised patients. This review aimed to provide an overview of hepatitis B vaccine non-response, the mechanisms involved, B cell amnesia, and strategies to overcome it. METHODS Databases, including Google Scholar, PubMed, Scopus, Cochrane, and ClinicalTrials.org, were used to search and retrieve articles using keywords on hepatitis B vaccine non-response and B cell amnesia. The PRISMA guideline was followed in identifying studies, screening, selection, and reporting of findings. RESULTS A total of 133 studies on hepatitis B vaccine non-response, mechanisms, and prevention/management strategies were included in the review after screening and final selection. Factors responsible for hepatitis B vaccine non-response were found to include genetic, immunological factors, and B cell amnesia in healthy individuals. The genetic factors were sex, HLA haplotypes, and genetic polymorphisms in immune response markers (cytokines). Non-response was common in conditions of immunodeficiency, such as renal failure, haemodialysis, celiac disease, inflammatory bowel disease, hepatitis C co-infection, and latent hepatitis B infection. Others included diabetes mellitus and HIV infection. The mechanisms involved were impaired immune response by suppression of response (T helper cells) or induced suppression of response (through regulatory B and T cells). DISCUSSION A comprehensive and careful understanding of the patient factors and the nature of the vaccine contributes to developing effective preventive measures. These include revaccination or booster dose, vaccine administration through the intradermal route, and the use of adjuvants in the vaccine.
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Affiliation(s)
- Nura Bello
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
- Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria 810107, Nigeria
| | - Shuaibu A. Hudu
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
- Department of Medical Microbiology and Parasitology, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria
| | - Ahmed S. Alshrari
- Medical Laboratory Technology Department, Faculty of Applied Medical Science, Northern Border University, Arar 91431, Saudi Arabia;
| | - Mustapha U. Imam
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
| | - Abdulgafar O. Jimoh
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
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Tahir A, Shinkafi SH, Alshrari AS, Yunusa A, Umar MT, Hudu SA, Jimoh AO. A Comprehensive Review of Hepatitis B Vaccine Nonresponse and Associated Risk Factors. Vaccines (Basel) 2024; 12:710. [PMID: 39066348 PMCID: PMC11281605 DOI: 10.3390/vaccines12070710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 06/10/2024] [Accepted: 06/14/2024] [Indexed: 07/28/2024] Open
Abstract
Hepatitis B virus (HBV) infection remains a significant global health concern worldwide, contributing to high rates of mortality and morbidity, including chronic hepatitis B, cirrhosis, and hepatocellular carcinoma (HCC). Universal vaccination programs have significantly reduced the rate of HBV transmission; however, a subset of individuals fail to develop a protective immune response following vaccination and are termed nonresponders. A comprehensive search strategy using the PubMed, Google Scholar, and Web of Science databases was employed to search for relevant studies using keywords including "hepatitis B vaccine", "vaccine nonresponse", "immunogenicity", "immune response to the hepatitis B vaccine", and "associated risk factors". Factors influencing the vaccine's response include demographic factors, such as age and sex, with increased nonresponse rates being observed in older adults and males. Obesity, smoking, and alcohol consumption are lifestyle factors that decrease the vaccine response. Medical conditions, including diabetes, chronic kidney and liver diseases, HIV, celiac disease, and inflammatory bowel disease, affect the vaccine response. Major histocompatibility complex (MHC) haplotypes and genetic polymorphisms linked to immune regulation are genetic factors that further influence the vaccine's effectiveness. To reduce the global burden of hepatitis B infection, it is essential to understand these factors to improve vaccine effectiveness and develop individualized vaccination strategies.
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Affiliation(s)
- Albashir Tahir
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840001, Nigeria; (A.T.); (A.Y.); (M.T.U.)
- Department of Pharmacology, Faculty of Basic Medical Sciences, Bauchi State University, Gadau 751105, Nigeria
| | - Sa’adatu Haruna Shinkafi
- Department of Microbiology and Parasitology, Usmanu Danfodiyo University Teaching Hospital, Sokoto 23270, Nigeria
| | - Ahmed Subeh Alshrari
- Medical Laboratory Technology Department, Faculty of Applied Medical Science, Northern Border University, Arar 91431, Saudi Arabia;
| | - Abdulmajeed Yunusa
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840001, Nigeria; (A.T.); (A.Y.); (M.T.U.)
| | - Muhammad Tukur Umar
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840001, Nigeria; (A.T.); (A.Y.); (M.T.U.)
| | - Shuaibu Abdullahi Hudu
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
- Department of Microbiology and Parasitology, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria
| | - Abdulgafar Olayiwola Jimoh
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840001, Nigeria; (A.T.); (A.Y.); (M.T.U.)
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Olakunde BO, Ifeorah IM, Adeyinka DA, Olakunde OA, Ogundipe T, Olawepo JO, Ezeanolue EE. Immune response to hepatitis B vaccine among children under 5 years in Africa: a meta-analysis. Trop Med Health 2024; 52:28. [PMID: 38561838 PMCID: PMC10983738 DOI: 10.1186/s41182-024-00594-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 03/17/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection in Africa is mostly acquired before the age of 5 years through vertical or horizontal routes. While all the countries in the World Health Organization African region have introduced HBV vaccination into their national immunization programs, the rate of protective immune response to HBV vaccine among children in Africa has not been systematically synthesized. In this study, we estimated the HBV vaccine seroprotection rate (defined as anti-HBs titer ≥ 10 IU/L) and the associated factors among under-five children who completed a primary series of HBV vaccination in Africa. METHODS We systematically searched PubMed, Web Science, and Scopus databases from inception to May 2022 for potentially eligible studies. The pooled seroprotection rate was estimated using a random-effects model with Freeman-Tukey double arcsine transformation and the associated factors were examined using odds ratio estimated by the DerSimonian and Laird method. RESULTS From the 1063 records identified, 29 studies with a total sample size of 9167 under-five children were included in the meta-analysis. The pooled seroprotection rate was 89.23% (95% CI 85.68-92.33%, I2 = 95.96%, p < 0.001). In the subgroup analyses, there was a significant difference in the rate by the assay method, vaccine dose, and vaccine combination. HIV-positive children had lower odds of achieving seroprotection when compared with HIV-negative children (OR = 0.22, 95%CI 0.12-0.40). CONCLUSIONS The majority of under-five children in Africa achieved seroprotection after completing three or four doses of HBV vaccine. However, the rate was lower among children living with HIV. This calls for interventions to timely identify and address nonresponse to HBV vaccine, particularly among immunosuppressed children.
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Affiliation(s)
- Babayemi O Olakunde
- Department of Community Prevention and Care Services, National Agency for the Control of AIDS, Abuja, Nigeria.
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria.
- Department of Population and Community Health, School of Public Health, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA.
| | - Ijeoma M Ifeorah
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Department of Medical Laboratory Sciences, University of Nigeria Nsukka, Enugu, Nigeria
| | - Daniel A Adeyinka
- Department of Research, Saskatchewan Health Authority, Saskatoon, SK, Canada
- Department of Public Health, Federal Ministry of Health, Abuja, Nigeria
| | - Olubunmi A Olakunde
- Department of Disease Control and Immunization, Ondo State Primary Health Care Development Agency, Ondo, Nigeria
| | | | - John O Olawepo
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Department of Health Sciences, Northeastern University, Boston, MA, USA
| | - Echezona E Ezeanolue
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Healthy Sunrise Foundation, Nevada, USA
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Al-Busafi SA, Alwassief A. Global Perspectives on the Hepatitis B Vaccination: Challenges, Achievements, and the Road to Elimination by 2030. Vaccines (Basel) 2024; 12:288. [PMID: 38543922 PMCID: PMC10975970 DOI: 10.3390/vaccines12030288] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 02/23/2024] [Accepted: 02/27/2024] [Indexed: 10/21/2024] Open
Abstract
Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths being attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). The HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the essential formidable challenges and facilitating factors for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.
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Affiliation(s)
- Said A. Al-Busafi
- Division of Gastroenterology and Hepatology, Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman
| | - Ahmed Alwassief
- Division of Gastroenterology and Hepatology, Department of Medicine, Sultan Qaboos University Hospital, Muscat 123, Oman
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Ou G, Qing L, Zhang L, Yang Y, Ye G, Peng L, Li Y, Yang L, Liu Y. Cytokine IL-5 and HGF: combined prediction of non-/low immune response to hepatitis B vaccination at birth in infants born to HBsAg-positive mothers. Front Cell Infect Microbiol 2024; 14:1332666. [PMID: 38495649 PMCID: PMC10940320 DOI: 10.3389/fcimb.2024.1332666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 02/19/2024] [Indexed: 03/19/2024] Open
Abstract
Background The immune response to hepatitis B vaccine may be influenced by numerous factors, and patients with non/low response re-exposed to hepatitis B virus remain susceptible. Thus, a better understanding of the underlying mechanisms of non/low immune response in infants born to Hepatitis B surface antigen (HBsAg)-positive mothers is essential. Methods 100 infants born to HBsAg-positive mothers from 2015 to 2020 were enrolled in the study, further divided into the non/low response group (n=13) and the moderate strong response group (n=87) based on the quantification of hepatitis B surface antibody at 12 months of age. The differential expression of 48 immune-related cytokines in the two groups was compared and analyzed in detail. The key cytokines were further identified and clinically predictive models were developed. Results We found that 13 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group, compared with the moderate strong response group at birth. In addition, 9 cytokines were lowly expressed and one cytokine was highly expressed in the non/low response group at 12 months of age. Furthermore, we found that IL-5 and HGF were promising predictors for predicting the immunization response to hepatitis B vaccine in infants, and the combination of the two cytokines showed the best predictive efficiency, with an area under the curve (AUC) value of 0.844. Conclusion The present study provides a theoretical basis on cytokines for developing and implementing effective immunotherapies against non/low immune response in infants born to HBsAg-positive mothers.
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Affiliation(s)
- Guanyong Ou
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
- School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Ling Qing
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
- Graduate Collaborative Training Base of Shenzhen Third People’s Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Li Zhang
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
- Graduate Collaborative Training Base of Shenzhen Third People’s Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Yang Yang
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Guoguo Ye
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Ling Peng
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Yanjie Li
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Liuqing Yang
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Yingxia Liu
- National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, The Third People’s Hospital of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
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10
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Geta M, Yizengaw E, Manyazewal T. Hepatitis B vaccine effectiveness among vaccinated children in Africa: a systematic review and meta-analysis. BMC Pediatr 2024; 24:145. [PMID: 38413906 PMCID: PMC10900737 DOI: 10.1186/s12887-024-04557-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 01/11/2024] [Indexed: 02/29/2024] Open
Abstract
BACKGROUND Globally, 257 million people have chronic hepatitis. Even though a safe and effective prophylactic vaccine against HBV infection has been available, it causes significant morbidity and mortality. HBV vaccines were designed to improve or modulate the host immune responses. The effectiveness of the vaccine is determined by measuring serum hepatitis B surface antibody (Anti-HBs) level. Therefore, this systematic review aimed to evaluate the effectiveness of hepatitis B vaccine among vaccinated children. METHODS Preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines was applied for systematically searching of different databases. Only cross-section studies measuring the level of anti-HBs of vaccinated children were included. The seroprotective level with anti-HBs > 10mIU/ml was extracted. The meta-analysis was performed using statistical software for data sciences (STATA) version 14. Effectiveness estimates were reported as a proportion of anti-HBs level. The heterogeneity between studies was evaluated using the I2 test, and I2 > 50% and/or P < 0.10 was considered significant heterogeneity. Significant publication bias was considered when Egger's test P-value < 0.10. The new castle Ottawa scale was used to assess the quality of the studies. RESULTS A pooled sample size of the included papers for meta-analysis was 7430. The pooled prevalence of seroprotected children was 56.95%, with a heterogeneity index (I2) of 99.4% (P < 0.001). 35% of the participants were hypo-responders (10-99mIU/ml) and 21.46% were good responders (> 100mIU/ml). Based on subgroup analysis using country of studies conducted, the highest prevalence of anti-HBs was 87.00% (95% CI: 84.56, 89.44), in South Africa, and the lowest was 51.99% (95% CI: 20.41-83.58), with a heterogeneity index I2 = 70.7% (p = 0.009) in Ethiopia. CONCLUSION AND RECOMMENDATIONS Hepatitis B vaccine seroprotective level in the current pooled analysis have suboptimal, which failed to demonstrate consistent effectiveness for global hepatitis B virus elimination plan in 2030. Using consistent age group may have a significant value for the decision of the HB vaccine effectiveness. A significant heterogeneity was observed both in studies conducted in Ethiopia and Egypt. Therefore, the impact of HB vaccination on the prevention of hepatitis B virus infection should be assessed regularly in those countries. Future meta-analysis is needed to investigate all possible vaccines in a separate way of reviewing, which will lead to a strong conclusion and recommendations.
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Affiliation(s)
- Mekuanint Geta
- Translational Medicine Program, Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
- Department of Medical Microbiology, School of Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
| | - Endalew Yizengaw
- Department of Laboratory Science, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia
| | - Tsegahun Manyazewal
- Translational Medicine Program, Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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11
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Naqid IA, Mosa AA, Ibrahim SV, Ibrahim NH, Hussein NR. Hepatitis B vaccination status and knowledge, attitude, and practice towards Hepatitis B virus among medical sciences students: A cross-sectional study. PLoS One 2023; 18:e0293822. [PMID: 37930973 PMCID: PMC10627443 DOI: 10.1371/journal.pone.0293822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 10/19/2023] [Indexed: 11/08/2023] Open
Abstract
BACKGROUND AND AIMS Healthcare staff are at high risk of occupational exposure to Hepatitis B and other blood-borne diseases. Lack of education about the knowledge of Hepatitis B virus contributes to an increase in cases. This study aims to determine the knowledge of the Hepatitis B virus among the medical professionals in Duhok province, Kurdistan Region of Iraq, and to determine their knowledge of the importance of vaccination. MATERIALS AND METHODS This cross-sectional study was conducted in Duhok province, Kurdistan Region of Iraq, among medical science students from November 2022 to February 2023 and a total of 511 students participated in the study. A Self-administered questionnaire comprising 22 items categorized into five sections was distributed to the students either electronically or by paper and pen method. The survey utilized a Five-point Likert scale when assessing respondents' opinions on knowledge, attitude, and practice (KAP). Microsoft Excel and GraphPad Prism 9 were used for statistical analysis. RESULTS A total of 511 responses were collected from medical, dental, pharmacy, and laboratory students. The average age of the participants was 20.74 ±1.43 years. Among the respondents, only 96 (18.8%) were fully vaccinated against the Hepatitis B virus (received 3 or more doses of the vaccine), while 294 (57.5%) were not vaccinated. Lack of vaccination programs was the major reason for not receiving a vaccination (n = 182, 62%). About 286 (55.96%) of the participants had good knowledge, attitude, and practice on Hepatitis B, manifesting median scores of 26, 18, and 20, respectively. CONCLUSION In our study, half of the students were found to be unvaccinated, mainly due to the absence of vaccination programs. Vaccinated students exhibited better knowledge, attitude, and practice toward the infection than non-vaccinated students. Therefore, we recommend the implementation of a vaccination program as well as training on infection prevention guidelines to increase awareness and encourage vaccination.
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Affiliation(s)
- Ibrahim A. Naqid
- Department of Biomedical Sciences, College of Medicine, University of Zakho, Zakho, Kurdistan Region, Iraq
| | - Ahmed A. Mosa
- Department of Biomedical Sciences, College of Medicine, University of Zakho, Zakho, Kurdistan Region, Iraq
| | - Shah Vahel Ibrahim
- Department of Biomedical Sciences, College of Medicine, University of Zakho, Zakho, Kurdistan Region, Iraq
| | - Nizar Hussein Ibrahim
- Department of Biomedical Sciences, College of Medicine, University of Zakho, Zakho, Kurdistan Region, Iraq
| | - Nawfal R. Hussein
- Department of Biomedical Sciences, College of Medicine, University of Zakho, Zakho, Kurdistan Region, Iraq
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12
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Gary EN, Tursi NJ, Warner BM, Cuismano G, Connors J, Parzych EM, Griffin BD, Bell MR, Ali AR, Frase D, Hojecki CE, Canziani GA, Chaiken I, Kannan T, Moffat E, Embury-Hyatt C, Wooton SK, Kossenkov A, Patel A, Kobasa D, Kutzler MA, Haddad EK, Weiner DB. Adenosine deaminase augments SARS-CoV-2 specific cellular and humoral responses in aged mouse models of immunization and challenge. Front Immunol 2023; 14:1138609. [PMID: 36999023 PMCID: PMC10043169 DOI: 10.3389/fimmu.2023.1138609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 02/23/2023] [Indexed: 03/16/2023] Open
Abstract
Despite numerous clinically available vaccines and therapeutics, aged patients remain at increased risk for COVID-19 morbidity. Furthermore, various patient populations, including the aged can have suboptimal responses to SARS-CoV-2 vaccine antigens. Here, we characterized vaccine-induced responses to SARS-CoV-2 synthetic DNA vaccine antigens in aged mice. Aged mice exhibited altered cellular responses, including decreased IFNγ secretion and increased TNFα and IL-4 secretion suggestive of TH2-skewed responses. Aged mice exhibited decreased total binding and neutralizing antibodies in their serum but significantly increased TH2-type antigen-specific IgG1 antibody compared to their young counterparts. Strategies to enhance vaccine-induced immune responses are important, especially in aged patient populations. We observed that co-immunization with plasmid-encoded adenosine deaminase (pADA)enhanced immune responses in young animals. Ageing is associated with decreases in ADA function and expression. Here, we report that co-immunization with pADA enhanced IFNγ secretion while decreasing TNFα and IL-4 secretion. pADA expanded the breadth and affinity SARS-CoV-2 spike-specific antibodies while supporting TH1-type humoral responses in aged mice. scRNAseq analysis of aged lymph nodes revealed that pADA co-immunization supported a TH1 gene profile and decreased FoxP3 gene expression. Upon challenge, pADA co-immunization decreased viral loads in aged mice. These data support the use of mice as a model for age-associated decreased vaccine immunogenicity and infection-mediated morbidity and mortality in the context of SARS-CoV-2 vaccines and provide support for the use of adenosine deaminase as a molecular adjuvant in immune-challenged populations.
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Affiliation(s)
- Ebony N. Gary
- The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States
| | - Nicholas J. Tursi
- The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Bryce M. Warner
- Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Gina Cuismano
- The Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA, United States
- The Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, United States
| | - Jennifer Connors
- The Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA, United States
- The Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, United States
| | - Elizabeth M. Parzych
- The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States
| | - Bryan D. Griffin
- Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
| | - Matthew R. Bell
- The Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA, United States
- The Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, United States
| | - Ali R. Ali
- The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States
| | - Drew Frase
- The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States
| | - Casey E. Hojecki
- The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States
| | - Gabriela A. Canziani
- The Department of Biochemistry, Drexel University college of Medicine, Philadelphia, PA, United States
| | - Irwin Chaiken
- The Department of Biochemistry, Drexel University college of Medicine, Philadelphia, PA, United States
| | - Toshitha Kannan
- The Genomics Core, The Wistar Institute, Philadelphia, PA, United States
| | - Estella Moffat
- National Center for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB, Canada
| | - Carissa Embury-Hyatt
- National Center for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, MB, Canada
| | - Sarah K. Wooton
- Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
| | - Andrew Kossenkov
- The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States
- The Genomics Core, The Wistar Institute, Philadelphia, PA, United States
| | - Ami Patel
- The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States
| | - Darwyn Kobasa
- Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
- Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
| | - Michele A. Kutzler
- The Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA, United States
- The Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, United States
| | - Elias K. Haddad
- The Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA, United States
- The Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, United States
| | - David B. Weiner
- The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States
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Kwon JY, Daoud ND, Hashash JG, Picco MF, Farraye FA. Efficacy of Hepatitis B Vaccination with a Novel Immunostimulatory Sequence Adjuvant (Heplisav-B) in Patients With Inflammatory Bowel Disease. Inflamm Bowel Dis 2023; 29:254-259. [PMID: 35468183 DOI: 10.1093/ibd/izac079] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Owing to the use of immunosuppressive agents, patients with inflammatory bowel disease (IBD) have an increased risk of vaccine preventable diseases, including infection with hepatitis B virus (HBV). Heplisav-B, an FDA-approved vaccine, is more effective (90% to 100%) than Engerix-B (70.5% to 90.2%) at inducing immunity to HBV in clinical studies. Available data on efficacy of Heplisav-B vaccine in patients with IBD are limited. METHODS This retrospective observational study included patients age 18 years and older with ulcerative colitis (UC) or Crohn's disease (CD) who received 1 or 2 doses of Heplisav-B vaccine and had postvaccination serologic testing. Prior to immunization, all participants were seronegative for HBsAb antibodies (HBsAb) measured as <10 IU/mL. Postvaccination HBsAb of ≥10 IU/mL was considered successful vaccination. Patient demographics, disease characteristics, and medications were abstracted. RESULTS One hundred six patients were included in the analysis. Median age was 43 years, and 44 (42%) were female. Thirty-nine patients (37%) had UC, whereas 67 (63%) had CD. Eighty-three patients (78.3%) had active immunity after vaccination with Heplisav-B, with median postvaccination HBsAb levels of 114 IU/L. Patients with chronic obstructive pulmonary disease, chronic kidney disease, diabetes mellitus, immunomodulator use, or those on 2 or more of immunosuppressive medications were less likely to respond to Heplisav-B, though these findings were not statistically significant on a multivariate analysis aside from chronic kidney disease. CONCLUSIONS Heplisav-B, a 2-dose vaccine, is an effective vaccine for HBV in patients with IBD. In our study, its overall efficacy (78.3%) is greater than that reported for the presently available 3-dose vaccination (Engerix) in patients with IBD.
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Affiliation(s)
- Joshua Y Kwon
- Department of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Nader D Daoud
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Jana G Hashash
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Michael F Picco
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
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14
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Elbahrawy A, Atalla H, Alboraie M, Alwassief A, Madian A, El Fayoumie M, Tabll AA, Aly HH. Recent Advances in Protective Vaccines against Hepatitis Viruses: A Narrative Review. Viruses 2023; 15:214. [PMID: 36680254 PMCID: PMC9862019 DOI: 10.3390/v15010214] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/03/2023] [Accepted: 01/07/2023] [Indexed: 01/15/2023] Open
Abstract
Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination is evident in the control of serious viral infections, such as smallpox and polio. Viruses that infect human livers are known as hepatitis viruses and are classified into five major types from A to E, alphabetically. Although infection with hepatitis A virus (HAV) is known to be self-resolving after rest and symptomatic treatment, there were 7134 deaths from HAV worldwide in 2016. In 2019, hepatitis B virus (HBV) and hepatitis C virus (HCV) resulted in an estimated 820,000 and 290,000 deaths, respectively. Hepatitis delta virus (HDV) is a satellite virus that depends on HBV for producing its infectious particles in order to spread. The combination of HDV and HBV infection is considered the most severe form of chronic viral hepatitis. Hepatitis E virus (HEV) is another orally transmitted virus, common in low- and middle-income countries. In 2015, it caused 44,000 deaths worldwide. Safe and effective vaccines are already available to prevent hepatitis A and B. Here, we review the recent advances in protective vaccines against the five major hepatitis viruses.
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Affiliation(s)
- Ashraf Elbahrawy
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Hassan Atalla
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Mohamed Alboraie
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Ahmed Alwassief
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
- Gastroenterology Unit, Department of Internal Medicine, Sultan Qaboos University Hospital, P.O. Box 50, Muscat 123, Oman
| | - Ali Madian
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Assiut 71524, Egypt
| | - Mohammed El Fayoumie
- Gastroenterology and Hepatology Unit, Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Ashraf A. Tabll
- Microbial Biotechnology Department, Biotechnology Research Institute, National Research Center, Giza 12622, Egypt
- Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo 11517, Egypt
| | - Hussein H. Aly
- Department of Virology II, National Institute of Infectious Diseases, Toyama1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan
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15
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Girndt M, Plüer M, Dellanna F, Michelsen AK, Beige J, Toussaint K, Wehweck HJ, Koch M, Hafezi Rachti S, Faust J, Bosselmann HP, Witzke O, Janssen RS. Immunogenicity and safety of a booster dose of the hepatitis B vaccine HepB-CpG (HEPLISAV-B®) compared with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in adults receiving hemodialysis who previously received hepatitis B vaccination and are not seroprotected: Results of a randomized, multicenter phase 3 study. Hum Vaccin Immunother 2022; 18:2136912. [PMID: 36269938 DOI: 10.1080/21645515.2022.2136912] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
This study compared the immunogenicity and safety of a booster dose of HepB-CpG (HEPLISAV-B® vaccine) with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in patients receiving chronic hemodialysis. This was a multicenter, randomized, open-label, phase 3 study of adults receiving hemodialysis with antibodies to HBsAg (anti-HBs) <10 mIU/mL at study entry. The objective was to compare the seroprotection rate (SPR) induced by HepB-CpG with HepB-Eng or HepB-AS04. The SPR was defined as the percentage of patients with anti-HBs ≥10 mIU/mL post-vaccination. At 20 sites in Germany, 155 participants were randomized: HepB-CpG = 54; HepB-Eng = 50; and HepB-AS04 = 51. Of the 149 participants in the modified intention-to-treat population, 76.5% had not previously responded to at least one series of hepatitis B vaccine. Based on a post hoc analysis, the SPR in HepB-CpG recipients (52.8%; 95% confidence interval [CI]: 38.6%, 66.7%) was significantly higher than in HepB-Eng recipients (32.6%; 95% CI: 19.5%, 48.0%), and non-inferior to that in HepB-AS04 recipients (43.1%; 95% CI: 29.3%, 57.8%). Local post-injection reactions occurred in significantly fewer HepB-CpG (9.3%) than HepB-AS04 recipients (31.4%; p = .007) and at a similar rate to HepB-Eng recipients (8.2%). Systemic post-injection reactions in HepB-CpG recipients (18.5%) were similar to the HepB-AS04 group (19.6%) and higher than in the HepB-Eng group (12.2%). In this difficult-to-immunize population, a booster dose of HepB-CpG induced significantly higher levels of seroprotection than HepB-Eng with a similar safety profile. The higher levels of immunogenicity were not accompanied by higher levels of local post-injection reactions compared with HepB-AS04.
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Affiliation(s)
- Matthias Girndt
- Department of Internal Medicine II, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | - Manfred Plüer
- Nephrology, KfH-Nierenzentrum Berlin-Neukölln, in Berlin-Neukölln, Germany
| | - Frank Dellanna
- Kidney and Dialysis Center, MVZ DaVita Rhein Ruhr, Düsseldorf, Germany
| | - Ann K Michelsen
- Internal Medicine, MVZ Lütten Klein, Nephrocare Rostock GmbH, Rostock, Germany
| | - Joachim Beige
- Department of Nephrology and Kuratorium for Dialysis and Transplantation Renal Unit, Hospital St. Georg, Martin-Luther-University Halle/Wittenberg, Leipzig, Germany
| | - Kai Toussaint
- Lipid Clinic, Nephrocare Hamburg-Barmbek, Hamburg, Germany
| | | | | | | | - Justus Faust
- Internal Medicinem Regulatory and Medical Affairs, Nephrologische Gemeinschaftspraxis, Mainz, Germany
| | - Hans-Peter Bosselmann
- Klinik für Nieren- und Hochdruckkrankheiten and Bereich Endokrinologie und Stoffwechselkrankheiten, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany
| | - Oliver Witzke
- Department of Infectious Diseases, West German Centre of Infectious Diseases, Universitätsmedizin Essen, University Duisburg-Essen, Essen, Germany
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- HBV-18 Study Investigators: Herman Haller, Medizinische Hochschule Hannover, Hannover, Germany; Clemens Grupp, Sozialstiftung Bamberg, Bamberg, Germany; Jens Passauer, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany; Gert-Peter Dragoun, KfH Nierenzentrum, Aschaffenburg, Germany; Thomas Strack, KfH Nierenzentrum Munich-Schwabing, Munich, Germany; Tobias Marsen, KfH Nierenzentrum, Cologne, Germany; Stefan Weiner, Krankenhaus der Barmherzigen Brüder, Nordallee, Germany; Norbert Bockreiss, KfH Nierenzentrum, Oberschleissheim, Germany
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16
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Nakai Y, Miyakawa K, Yamaoka Y, Hatayama Y, Nishi M, Suzuki H, Kimura H, Takahashi H, Kimura Y, Ryo A. Generation and Utilization of a Monoclonal Antibody against Hepatitis B Virus Core Protein for a Comprehensive Interactome Analysis. Microorganisms 2022; 10:microorganisms10122381. [PMID: 36557634 PMCID: PMC9783060 DOI: 10.3390/microorganisms10122381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/22/2022] [Accepted: 11/29/2022] [Indexed: 12/05/2022] Open
Abstract
Hepatitis B virus (HBV) core antigen (HBc) is a structural protein that forms the viral nucleocapsid and is involved in various steps of the viral replication cycle, but its role in the pathogenesis of HBV infection is still elusive. In this study, we generated a mouse monoclonal antibody (mAb) against HBc and used it in antibody-based in situ biotinylation analysis in order to identify host proteins that interact with HBc. HBc antigen was produced with a wheat germ cell-free protein synthesis system and used to immunize mice. Among the established hybridoma clones, a single clone (mAb #7) was selected and further characterized for its ability in the antibody-based in situ biotinylation analysis to collect host proteins that are in the vicinity of HBc. Using mass spectrometry, we identified 215 HBc-interacting host proteins, three of which bind HBc most significantly under hypoxic conditions. Our results indicate that mAb #7 can be used to systematically identify host proteins that interact with HBc under pathophysiological conditions, and thus may be useful to explore the molecular pathways involved in HBV-induced cytopathogenesis.
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Affiliation(s)
- Yusuke Nakai
- Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
- Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan
| | - Kei Miyakawa
- Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Yutaro Yamaoka
- Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
- Life Science Laboratory, Technology and Development Division, Kanto Chemical Co., Inc., Isehara 259-1146, Japan
| | - Yasuyoshi Hatayama
- Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
- Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan
| | - Mayuko Nishi
- Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Hidefumi Suzuki
- Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Hirokazu Kimura
- Department of Health Science, Gunma Paz University Graduate School, Takasaki 370-0006, Japan
| | - Hidehisa Takahashi
- Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Yayoi Kimura
- Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan
| | - Akihide Ryo
- Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
- Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan
- Correspondence: ; Tel.: +81-45-787-2602
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17
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Evaluation of a personalized, dose-sparing revaccination strategy in hepatitis B vaccine non-responders. Vaccine 2022; 40:3210-3215. [DOI: 10.1016/j.vaccine.2022.04.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Revised: 03/10/2022] [Accepted: 04/11/2022] [Indexed: 11/23/2022]
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Nicoli F, Mantelli B, Gallerani E, Telatin V, Squarzon L, Masiero S, Gavioli R, Palù G, Barzon L, Caputo A. Effects of the age of vaccination on the humoral responses to a human papillomavirus vaccine. NPJ Vaccines 2022; 7:37. [PMID: 35292655 PMCID: PMC8924199 DOI: 10.1038/s41541-022-00458-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 02/11/2022] [Indexed: 11/11/2022] Open
Abstract
Adult vaccination programs are receiving increasing attention however, little is known regarding the impact of age on the maintenance of the immune response. We investigated this issue in the context of a human papillomavirus (HPV) vaccination program collecting real-world data on the durability of humoral immunity in 315 female subjects stratified according to vaccination age (adolescents and adults) and sampled at early or late time points after the last vaccine dose. HPV-specific IgGs, but not memory B cells, were induced and maintained at higher levels in subjects vaccinated during adolescence. Nonetheless, antibody functions waned over time to a similar degree in adolescents and adults. To shed light on this phenomena, we analyzed quantitative and qualitative properties of lymphocytes. Similar biochemical features were observed between B-cell subsets from individuals belonging to the two age groups. Long term humoral responses toward vaccines administered at an earlier age were comparably maintained between adolescents and adults. The percentages of naïve B and CD4+ T cells were significantly higher in adolescents, and the latter directly correlated with IgG titers against 3 out of 4 HPV types. Our results indicate that age-specific HPV vaccine responsiveness is mostly due to quantitative differences of immune cell precursors rather than qualitative defects in B cells. In addition, our results indicate that adults also have a good humoral immunogenic profile, suggesting that their inclusion in catch-up programmes is desirable.
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Affiliation(s)
- Francesco Nicoli
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121, Ferrara, Italy
- Department of Molecular Medicine, University of Padova, 35121, Padova, Italy
| | - Barbara Mantelli
- Department of Molecular Medicine, University of Padova, 35121, Padova, Italy
| | - Eleonora Gallerani
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121, Ferrara, Italy
| | - Valentina Telatin
- Department of Molecular Medicine, University of Padova, 35121, Padova, Italy
| | - Laura Squarzon
- Department of Molecular Medicine, University of Padova, 35121, Padova, Italy
| | - Serena Masiero
- Department of Molecular Medicine, University of Padova, 35121, Padova, Italy
| | - Riccardo Gavioli
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121, Ferrara, Italy
| | - Giorgio Palù
- Department of Molecular Medicine, University of Padova, 35121, Padova, Italy
| | - Luisa Barzon
- Department of Molecular Medicine, University of Padova, 35121, Padova, Italy
| | - Antonella Caputo
- Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121, Ferrara, Italy.
- Department of Molecular Medicine, University of Padova, 35121, Padova, Italy.
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19
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Han B, Liu W, Du J, Liu H, Zhao T, Yang S, Wang S, Zhang S, Liu B, Liu Y, Cui F. 12 Months Persistent Immunogenicity after Hepatitis B Vaccination in Patients with Type 2 Diabetes and Immunogenicity of Revaccination in Non-Responders: An Open-Label Randomized Controlled Trial. Vaccines (Basel) 2021; 9:1407. [PMID: 34960153 PMCID: PMC8705985 DOI: 10.3390/vaccines9121407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/22/2021] [Accepted: 11/26/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND In initial studies, the immunogenicity and safety of hepatitis B vaccines in patients with diabetes has been assessed in China. METHODS In six township health centers in Gansu Province, 232 diabetic patients and 77 healthy people were allocated to receive two 3-dose hepatitis B vaccines (Group D20SC 0-1-6; Group D20CHO 0-1-6; Group ND20SC 0-1-6). Participants were followed up at 12 months after being fully vaccinated. One dose of the vaccine was randomly administered to non-responders. Chi-square test was used to compare the differences in response rate between two groups. RESULTS The anti-HBs response rates of three groups decreased from 84.1%, 89.1% and 88.3% at one month to 64.6%, 79.8% and 71.4% at twelve months. There was no statistical difference in the immune response rates between Group D20SC 0-1-6 and Group ND20SC 0-1-6; however, that of Group D20CHO 0-1-6 was higher than that of Group D20SC 0-1-6. After revaccination, the geometric mean concentrations were 491.7 mIU/mL and 29.7 mIU/mL after using vaccines containing 60 μg and 20 μg HBsAg. CONCLUSIONS At 12 months, immune response in diabetic patients were not significantly different from that in healthy people. Revaccination with one dose of hepatitis B vaccine containing 60 μg HBsAg for non-responders was more satisfactory.
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Affiliation(s)
- Bingfeng Han
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China; (B.H.); (H.L.); (T.Z.); (S.Z.)
| | - Wu Liu
- Jingyuan County Center for Disease Control and Prevention, Baiyin 730600, China; (W.L.); (S.Y.)
| | - Juan Du
- Department of Laboratorial Science and Technology & Vaccine Research Center, School of Public Health, Peking University, Beijing 100191, China; (J.D.); (B.L.); (Y.L.)
| | - Hanyu Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China; (B.H.); (H.L.); (T.Z.); (S.Z.)
| | - Tianshuo Zhao
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China; (B.H.); (H.L.); (T.Z.); (S.Z.)
| | - Shubo Yang
- Jingyuan County Center for Disease Control and Prevention, Baiyin 730600, China; (W.L.); (S.Y.)
| | - Shuai Wang
- Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China;
| | - Sihui Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China; (B.H.); (H.L.); (T.Z.); (S.Z.)
| | - Bei Liu
- Department of Laboratorial Science and Technology & Vaccine Research Center, School of Public Health, Peking University, Beijing 100191, China; (J.D.); (B.L.); (Y.L.)
| | - Yaqiong Liu
- Department of Laboratorial Science and Technology & Vaccine Research Center, School of Public Health, Peking University, Beijing 100191, China; (J.D.); (B.L.); (Y.L.)
| | - Fuqiang Cui
- Department of Laboratorial Science and Technology & Vaccine Research Center, School of Public Health, Peking University, Beijing 100191, China; (J.D.); (B.L.); (Y.L.)
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20
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Weinberger B. Vaccination of older adults: Influenza, pneumococcal disease, herpes zoster, COVID-19 and beyond. Immun Ageing 2021; 18:38. [PMID: 34627326 PMCID: PMC8501352 DOI: 10.1186/s12979-021-00249-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 09/21/2021] [Indexed: 12/11/2022]
Abstract
Preserving good health in old age is of utmost importance to alleviate societal, economic and health care-related challenges caused by an aging society. The prevalence and severity of many infectious diseases is higher in older adults, and in addition to the acute disease, long-term sequelae, such as exacerbation of underlying chronic disease, onset of frailty or increased long-term care dependency, are frequent. Prevention of infections e.g. by vaccination is therefore an important measure to ensure healthy aging and preserve quality of life. Several vaccines are specifically recommended for older adults in many countries, and in the current SARS-CoV-2 pandemic older adults were among the first target groups for vaccination due to their high risk for severe disease. This review highlights clinical data on the influenza, Streptococcus pneumoniae and herpes zoster vaccines, summarizes recent developments to improve vaccine efficacy, such as the use of adjuvants or higher antigen dose for influenza, and gives an overview of SARS-CoV-2 vaccine development for older adults. Substantial research is ongoing to further improve vaccines, e.g. by developing universal influenza and pneumococcal vaccines to overcome the limitations of the current strain-specific vaccines, and to develop novel vaccines against pathogens, which cause considerable morbidity and mortality in older adults, but for which no vaccines are currently available. In addition, we need to improve uptake of the existing vaccines and increase awareness for life-long vaccination in order to provide optimal protection for the vulnerable older age group.
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Affiliation(s)
- Birgit Weinberger
- Institute for Biomedical Aging Research, Universität Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.
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21
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Vesikari T, Finn A, van Damme P, Leroux-Roels I, Leroux-Roels G, Segall N, Toma A, Vallieres G, Aronson R, Reich D, Arora S, Ruane PJ, Cone CL, Manns M, Cosgrove C, Faust SN, Ramasamy MN, Machluf N, Spaans JN, Yassin-Rajkumar B, Anderson D, Popovic V, Diaz-Mitoma F. Immunogenicity and Safety of a 3-Antigen Hepatitis B Vaccine vs a Single-Antigen Hepatitis B Vaccine: A Phase 3 Randomized Clinical Trial. JAMA Netw Open 2021; 4:e2128652. [PMID: 34636914 PMCID: PMC8511978 DOI: 10.1001/jamanetworkopen.2021.28652] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
IMPORTANCE There is a need for improved immunogenicity of hepatitis B virus (HBV) vaccines among young adults with risk of infection. OBJECTIVES To demonstrate manufacturing equivalence of a 3-antigen (3A) HBV vaccine, evaluate noninferiority of seroprotection rate (SPR) of 3A-HBV vs single-antigen (1A) HBV after 2 and 3 vaccine doses, and compare safety and reactogenicity between 3A-HBV and 1A-HBV vaccines. DESIGN, SETTING, AND PARTICIPANTS This phase 3, double-blinded, randomized clinical trial included healthy adults aged 18 to 45 years randomized to 1 of three 3A-HBV groups or 1 control group receiving 1A-HBV. The trial was conducted at 37 community clinics and academic hospitals in Canada, Europe, the United Kingdom, and the United States between December 2017 and October 2019. Participants were followed up for 48 weeks after the first vaccination. INTERVENTIONS Intramuscular administration of 3A-HBV (10 μg) or 1A-HBV (20 μg) on days 0, 28, and 168. MAIN OUTCOMES AND MEASURES Geometric mean concentration (GMC) of serum hepatitis B surface antibodies (anti-HBs) and proportion of participants achieving seroprotection. RESULTS Of 2838 participants, 1638 (57.8%) were women, 2595 (91.5%) were White, and 161 (5.7%) were Black or African American. A total of 712 participants (25.1%) were randomized to the 1A-HBV group and 2126 (74.9%) to 3A-HBV. The mean (SD) age at informed consent was 33.5 (8.0) years. The study demonstrated 3A-HBV lot-to-lot consistency, as the 2-sided 95% CIs for each pairwise comparison for the anti-HBs GMC ratios were within 0.67 and 1.50 (eg, adjusted GMC ratio, lot A vs lot B: 0.82; 95% CI, 0.67-1.00; lot A vs lot C: 0.95; 95% CI, 0.78-1.15; lot B vs lot C: 1.16; 95% CI, 0.95-1.41). The SPR of the pooled 3A-HBV was noninferior to 1A-HBV and higher than 1A-HBV after 2 vaccinations at day 168 (90.4% [95% CI, 89.0%-91.8%] vs 51.6% [95% CI, 47.5%-55.6%]) and 3 vaccinations at day 196 (99.3% [95% CI, 98.7%-99.6%] vs 94.8% [95% CI, 92.7%-96.4%]). The mean GMC of anti-HBs with 3A-HBV was 7.9 times higher after 2 vaccinations at day 168 and 3.5 times higher after 3 vaccinations at day 196 compared with 1A-HBV (after 2 vaccinations, 3A-HBV: GMC, 118.7 mIU/mL; 95% CI, 108.0-129.0 mIU/mL; SE, 1.0 mIU/mL; 1A-HBV: GMC, 15.0 mIU/mL; 95% CI, 12.9-17.5 mIU/mL; SE, 1.0 mIU/mL; after 3 vaccinations, 3A-HBV: GMC, 5442.4 mIU/mL; 95% CI, 4967.0-5963.0 mIU/mL; SE, 1.0 mIU/mL; 1A-HBV: 1567.2 mIU/mL; 95% CI, 1338.0-1834.0 mIU/mL; SE, 1.0 mIU/mL). Rates of local and systemic reactogenicities were higher with 3A-HBV compared with 1A-HBV (local: 1805 of 2124 [85.0%] vs 469 of 712 [65.9%]; systemic: 1445 [68.0%] vs 428 [60.1%]). Vaccine discontinuation due to adverse events (AE) was uncommon, and serious AEs were infrequent, reported in 42 participants (2.0%) and 3 participants (0.4%) in the 3A-HBV and 1A-HBV groups, respectively. CONCLUSIONS AND RELEVANCE In this study, consistently higher antibody concentrations and SPRs were found with 3A-HBV after 2 and 3 doses vs 1A-HBV in adults aged 18 to 45 years old. The safety and efficacy of 3A-HBV shows its usefulness for the prevention of hepatitis B in young healthy adults. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT03408730; EU Clinical Trials Number: 2017-001820-22.
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Affiliation(s)
| | - Adam Finn
- Bristol Royal Hospital for Children, Bristol, United Kingdom
| | - Pierre van Damme
- University of Antwerp–Center for the Evaluation of Vaccination, Universiteitsplein, Wilrijk, Belgium
| | | | | | | | - Azhar Toma
- Manna Research, Toronto, Ontario, Canada
| | | | - Ronnie Aronson
- LMC Diabetes and Endocrinology, Toronto, Ontario, Canada
| | | | | | - Peter J. Ruane
- Ruane Clinical Research Group Inc, Los Angeles, California
| | | | - Michael Manns
- Medizinishe Hochschule, Hannover, Lower Saxony, Germany
| | - Catherine Cosgrove
- St George’s University Hospital NHS Foundation Trust, London, United Kingdom
| | - Saul N. Faust
- NIHR Southampton Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
- Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom
| | - Maheshi N. Ramasamy
- Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital and University of Oxford, Oxford, United Kingdom
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22
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Schwarz T, Tober-Lau P, Hillus D, Helbig ET, Lippert LJ, Thibeault C, Koch W, Landgraf I, Michel J, Bergfeld L, Niemeyer D, Mühlemann B, Conrad C, Dang-Heine C, Kasper S, Münn F, Kappert K, Nitsche A, Tauber R, Schmidt S, Kopankiewicz P, Bias H, Seybold J, von Kalle C, Jones TC, Suttorp N, Drosten C, Sander LE, Corman VM, Kurth F. Delayed Antibody and T-Cell Response to BNT162b2 Vaccination in the Elderly, Germany. Emerg Infect Dis 2021; 27:2174-2178. [PMID: 34102097 PMCID: PMC8314803 DOI: 10.3201/eid2708.211145] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
We detected delayed and reduced antibody and T-cell responses after BNT162b2 vaccination in 71 elderly persons (median age 81 years) compared with 123 healthcare workers (median age 34 years) in Germany. These data emphasize that nonpharmaceutical interventions for coronavirus disease remain crucial and that additional immunizations for the elderly might become necessary.
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23
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Comparative cost-effectiveness of a 2-dose versus 3-dose vaccine for hepatitis B prevention in selected adult populations. Vaccine 2021; 39:4733-4741. [PMID: 34030898 DOI: 10.1016/j.vaccine.2021.05.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 05/05/2021] [Accepted: 05/07/2021] [Indexed: 12/22/2022]
Abstract
The hepatitis B virus is highly infectious and can cause incurable liver disease, leading to high morbidity rates, increased healthcare utilization, and high mortality. Multiple preventative hepatitis B vaccine options have been available for decades, but adherence to the traditional 6-month vaccine schedule for the approved 3-dose series remains low in adult populations at risk of hepatitis B exposure. A 2-dose hepatitis B vaccine (HEPLISAV-B) approved by the US Food and Drug Administration in 2017 induces rapid seroprotection within 1 month and has a safety profile comparable to a commonly used 3-dose vaccine. In a previous cost-effectiveness study, HEPLISAV-B had a favorable cost-effectiveness profile for multiple at-risk populations. The goal of the current analysis was to update and extend previous findings by evaluating cost-effectiveness of HEPLISAV-B compared with a 3-dose vaccine (Engerix-B) in selected adult populations, including patients with diabetes, chronic liver or kidney disease, end-stage renal disease, healthcare personnel, travelers to countries with endemic hepatitis B, and a public health population. Cost-effectiveness was measured as incremental cost-effectiveness ratios using a health economics Markov model that accounts for adherence rates, seroprotection rates, healthcare costs, and current pricing considerations. Patients progressed between a series of health states, and the difference in lifetime spending and survival for individuals receiving either HEPLISAV-B or Engerix-B was estimated from the perspective of a US managed care payer, HEPLISAV-B had favorable cost-effectiveness profiles for patients with diabetes, healthcare personnel, travelers, and patients with chronic liver disease and dominant incremental cost-effectiveness ratios for patients with chronic kidney disease and end-stage renal disease. A probabilistic sensitivity analysis supported the robustness of the cost-effectiveness profiles, and an additional analysis indicated that HEPLISAV-B was cost-effective in the general adult population. Overall, HEPLISAV-B was cost-effective in multiple adult populations recommended for HBV vaccination in the United States.
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24
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Reens AL, Cabral DJ, Liang X, Norton JE, Therien AG, Hazuda DJ, Swaminathan G. Immunomodulation by the Commensal Microbiome During Immune-Targeted Interventions: Focus on Cancer Immune Checkpoint Inhibitor Therapy and Vaccination. Front Immunol 2021; 12:643255. [PMID: 34054810 PMCID: PMC8155485 DOI: 10.3389/fimmu.2021.643255] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 04/22/2021] [Indexed: 12/11/2022] Open
Abstract
Emerging evidence in clinical and preclinical studies indicates that success of immunotherapies can be impacted by the state of the microbiome. Understanding the role of the microbiome during immune-targeted interventions could help us understand heterogeneity of treatment success, predict outcomes, and develop additional strategies to improve efficacy. In this review, we discuss key studies that reveal reciprocal interactions between the microbiome, the immune system, and the outcome of immune interventions. We focus on cancer immune checkpoint inhibitor treatment and vaccination as two crucial therapeutic areas with strong potential for immunomodulation by the microbiota. By juxtaposing studies across both therapeutic areas, we highlight three factors prominently involved in microbial immunomodulation: short-chain fatty acids, microbe-associate molecular patterns (MAMPs), and inflammatory cytokines. Continued interrogation of these models and pathways may reveal critical mechanistic synergies between the microbiome and the immune system, resulting in novel approaches designed to influence the efficacy of immune-targeted interventions.
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Affiliation(s)
- Abigail L. Reens
- Exploratory Science Center, Merck & Co., Inc., Cambridge, MA, United States
| | - Damien J. Cabral
- Exploratory Science Center, Merck & Co., Inc., Cambridge, MA, United States
| | - Xue Liang
- Exploratory Science Center, Merck & Co., Inc., Cambridge, MA, United States
| | - James E. Norton
- Exploratory Science Center, Merck & Co., Inc., Cambridge, MA, United States
| | - Alex G. Therien
- Exploratory Science Center, Merck & Co., Inc., Cambridge, MA, United States
| | - Daria J. Hazuda
- Exploratory Science Center, Merck & Co., Inc., Cambridge, MA, United States
- Infectious Disease and Vaccine Research, Merck & Co., Inc., West Point, PA, United States
| | - Gokul Swaminathan
- Exploratory Science Center, Merck & Co., Inc., Cambridge, MA, United States
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25
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COVID-19 dynamics after a national immunization program in Israel. Nat Med 2021; 27:1055-1061. [PMID: 33875890 DOI: 10.1038/s41591-021-01337-2] [Citation(s) in RCA: 129] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 04/05/2021] [Indexed: 01/19/2023]
Abstract
Studies on the real-life effect of the BNT162b2 vaccine for Coronavirus Disease 2019 (COVID-19) prevention are urgently needed. In this study, we conducted a retrospective analysis of data from the Israeli Ministry of Health collected between 28 August 2020 and 24 February 2021. We studied the temporal dynamics of the number of new COVID-19 cases and hospitalizations after the vaccination campaign, which was initiated on 20 December 2020. To distinguish the possible effects of the vaccination on cases and hospitalizations from other factors, including a third lockdown implemented on 8 January 2021, we performed several comparisons: (1) individuals aged 60 years and older prioritized to receive the vaccine first versus younger age groups; (2) the January lockdown versus the September lockdown; and (3) early-vaccinated versus late-vaccinated cities. A larger and earlier decrease in COVID-19 cases and hospitalization was observed in individuals older than 60 years, followed by younger age groups, by the order of vaccination prioritization. This pattern was not observed in the previous lockdown and was more pronounced in early-vaccinated cities. Our analysis demonstrates the real-life effect of a national vaccination campaign on the pandemic dynamics.
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26
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Tejada-Pérez JJ, Vázquez-Vicente JJ, Herrera-Burgos MR, Martín-Martín FG, Parrón-Carreño T, Alarcón-Rodríguez R. Fendrix ® Vaccine Effectiveness in Healthcare Workers Who Are Non-Responsive to Engerix B ® Vaccination. Vaccines (Basel) 2021; 9:vaccines9030279. [PMID: 33808589 PMCID: PMC8003400 DOI: 10.3390/vaccines9030279] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/13/2021] [Accepted: 03/16/2021] [Indexed: 11/24/2022] Open
Abstract
Hepatitis B (HBV) is a pathogen virus with transmission mechanisms that include contact with the infected blood or bodily fluids of the infected organism. Nowadays, healthcare workers are one of the most exposed groups to HBV. Conventionally, completing a vaccine series dosage with Engerix B® lowers this risk by providing workers with immunity to the virus. However, through the years, we have encountered nonresponsive health personnel to the Engerix B® vaccine; hence, the Occupational Health Service of Poniente Hospital studied the Fendrix® adjuvanted vaccine as an alternative vaccine to develop immunological responses in healthcare workers who do not respond to vaccination with Engerix B®. In our study, we employed a vaccination schedule with the Fendrix® vaccine, performing serology tests on the cases after the application of each dose. The results obtained showed humoral immunity in 92.3% of the cases, with a remarkable increase in antibody titer after the first doses. These encouraging results support the future inclusion of this vaccine as one possible alternative for the immunization to HBV for healthcare workers nonresponsive to Engerix B®.
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Affiliation(s)
- Juan José Tejada-Pérez
- Faculty of Health Sciences, University of Almería, Carr. Sacramento, s/n, 04120 La Cañada, Almeria, Spain; (T.P.-C.); (R.A.-R.)
- Correspondence:
| | - Juan José Vázquez-Vicente
- Risk Prevention Service, Poniente Hospital Entrepreneurial Public Health Agency, Ctra Almerimar, 31, 04700 El Ejido, Almeria, Spain; (J.J.V.-V.); (M.R.H.-B.); (F.G.M.-M.)
| | - María Renée Herrera-Burgos
- Risk Prevention Service, Poniente Hospital Entrepreneurial Public Health Agency, Ctra Almerimar, 31, 04700 El Ejido, Almeria, Spain; (J.J.V.-V.); (M.R.H.-B.); (F.G.M.-M.)
| | - Francisco Gabriel Martín-Martín
- Risk Prevention Service, Poniente Hospital Entrepreneurial Public Health Agency, Ctra Almerimar, 31, 04700 El Ejido, Almeria, Spain; (J.J.V.-V.); (M.R.H.-B.); (F.G.M.-M.)
| | - Tesifón Parrón-Carreño
- Faculty of Health Sciences, University of Almería, Carr. Sacramento, s/n, 04120 La Cañada, Almeria, Spain; (T.P.-C.); (R.A.-R.)
| | - Raquel Alarcón-Rodríguez
- Faculty of Health Sciences, University of Almería, Carr. Sacramento, s/n, 04120 La Cañada, Almeria, Spain; (T.P.-C.); (R.A.-R.)
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27
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Lebossé F, Zoulim F. [Hepatitis B vaccine and liver cancer]. Bull Cancer 2020; 108:90-101. [PMID: 33358507 DOI: 10.1016/j.bulcan.2020.10.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 10/01/2020] [Accepted: 10/02/2020] [Indexed: 02/06/2023]
Abstract
Hepatitis B Virus (HBV) chronic infection contributes to a high risk of hepatocellular cancer (HCC) development. HBV is a strong cancer inducer, due to natural history of infection, virological characteristics and viral DNA integrations events in host genome. Prolonged infection and high viral loads, particularly frequent in patients infected in childhood, are risk factors of HCC development for patients with HBV chronic infection. A HBV vaccine, based on immunization against the surface protein HBs, showed a strong efficacy to prevent chronic HBV infection. The development of universal neonatal vaccination programmes contributed to the decrease of HBV chronic infection incidence in children of high endemic areas. Although HBs antibodies levels diminished years after vaccination, HBV neonatal vaccination programmes led to a lower incidence of chronic HBV infection among young adults. The decrease of HBV chronic infection incidence was associated to a reduction of HCC incidence in children and young adults from areas with a high prevalence of HBV infection.
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Affiliation(s)
- Fanny Lebossé
- Hôpital de la Croix-Rousse, hospices civils de Lyon, service d'hépatologie, Lyon, France; Centre de recherche en cancérologie de Lyon, Lyon, France; Université Claude-Bernard Lyon 1, Lyon, France.
| | - Fabien Zoulim
- Hôpital de la Croix-Rousse, hospices civils de Lyon, service d'hépatologie, Lyon, France; Centre de recherche en cancérologie de Lyon, Lyon, France; Université Claude-Bernard Lyon 1, Lyon, France
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28
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Meier MA, Berger CT. A simple clinical score to identify likely hepatitis B vaccination non-responders - data from a retrospective single center study. BMC Infect Dis 2020; 20:891. [PMID: 33238923 PMCID: PMC7690196 DOI: 10.1186/s12879-020-05634-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 11/19/2020] [Indexed: 12/16/2022] Open
Abstract
Background About 10% of Hepatitis B vaccinated individuals mount no protective antibody levels against the hepatitis B surface antigen (HBs-Ag). Older age at primary immunization, obesity and smoking have previously been reported as risk factors associated with vaccine non-response. Here we tested whether these factors alone may allow selecting subjects that benefit from individualized immunization schedules. Methods Retrospective database analysis screening > 15,000 individual anti-HBs-IgG measurements. Non-responders (NR; anti-HBs-IgG < 10 IU/L) and low-responders (LR; anti-HBs-IgG 10–100 IU/L) were identified. Vaccine type, demographics, lifestyle, and immunological factors (leucocyte subset counts) were compared between NR, LR, and responders (R). Results We identified 113 LR/NR and compared them to 134 vaccine responders. We confirmed higher median age at primary vaccination (24.0 (R) vs. 30.5 (NR) vs. 31 (LR) years, p = 0.001), higher median BMI (23.2 kg/m2 (R) vs. 23.4 kg/m2 (NR) vs. 25.1 kg/m2 (LR), p = 0.001) and being a smoker (% smokers: 30.8% (R) vs. 57.1% (NR) vs. 52.5% (LR), p = 0.01) as factors negatively associated with anti-HBs-IgG levels. In a ROC analysis including these factors in a 6-point score, a high score predicted non-response with a specificity of 85% but at low sensitivity (47%). Conclusion A simple clinical risk score based on age, obesity, and smoking identifies individuals with a high likelihood of vaccine failure. Non-responders with a low score are candidates for in-depth analyses to better understand the immunological causes of HBV vaccine non-response. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-020-05634-y.
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Affiliation(s)
- Marc A Meier
- Vaccination Clinic, Medical Outpatient Unit, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
| | - Christoph T Berger
- Vaccination Clinic, Medical Outpatient Unit, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland. .,Translational Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
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Esaulenko EV, Yakovlev AA, Volkov GA, Sukhoruk AA, Surkov KG, Kruglyakov PV, Diaz-Mitoma F. Efficacy and Safety of a 3-Antigen (Pre-S1/Pre-S2/S) Hepatitis B Vaccine: Results of a Phase 3 randomized clinical trial in the Russian Federation. Clin Infect Dis 2020; 73:e3333-e3339. [PMID: 33119068 PMCID: PMC8563202 DOI: 10.1093/cid/ciaa1649] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/23/2020] [Indexed: 01/14/2023] Open
Abstract
Background This study compares the immunogenicity and safety of a 3-antigen (S/pre-S1/pre-S2) hepatitis B (HepB) vaccine (3AV), to a single antigen vaccine (1AV) in adults to support the registration of 3AV in Russia. Methods We conducted a randomized, double-blind, comparative study of 3-dose regimens of 3AV (10 μg) and 1AV (20 µg) in adults aged 18–45 years. We evaluated immunogenicity based on hepatitis B surface (HBs) antibody titers at days 1, 28, 90, 180, and 210, adverse and serious adverse events (SAEs) to study day 210. The primary outcome was based on the difference in rates of seroconversion at day 210 (lower bound 95% confidence interval [CI]: > − 4%). Secondary outcomes were seroprotection rates (SPR), defined as anti-HBs ≥10 mIU/mL and anti-HBs geometric mean concentration (GMC). Results Rate of seroconversion in 3AV (100%) was noninferior to 1AV (97.9%) at study day 210 (difference: 2.1%, 95% CI: −2.0, 6.3%]) but significantly higher at study day 28. SPR at study day 210 was >97% in both arms. Anti-HBs titers were significantly higher at study days 90 (P = .001) and 180 (P = .0001) with 3AV. Sex, age, and body mass index (BMI) had no impact on anti-HBs titers. The rates of local reactions related to vaccination were similar between vaccine arms (3AV vs 1AV) after the first (30% vs 18.8%, P = .15), second (20.0% vs 14.6%, P = .33), and third vaccination (14.9% vs 23.4%, P = .22). No SAEs were reported. Conclusions 3AV was noninferior to 1AV. 3AV induced high SPR, and there were no safety concerns. Clinical Trials Registration. NCT04209400.
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Affiliation(s)
- Elena V Esaulenko
- Federal State Budgetary Educational Institution of Higher Education; Saint Petersburg State Paediatric Medical University of the Ministry of Health of the Russian Federation
| | - Aleksey A Yakovlev
- St Petersburg State Budgetary Healthcare Institution; S.P. Botkin Clinical Infectious Diseases Hospital
| | | | - Anastasia A Sukhoruk
- Federal State Budgetary Educational Institution of Higher Education; Saint Petersburg State Paediatric Medical University of the Ministry of Health of the Russian Federation
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Zhang L, Yu C, Ge Z, Tao H, Meng F, Xu X, Tian T, Song C, Hu Z, Li J, Zhu F. Whole exome sequencing reveals the different responsiveness to Enterovirus 71 vaccination in Chinese children. Int J Infect Dis 2020; 97:47-53. [DOI: 10.1016/j.ijid.2020.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 06/04/2020] [Accepted: 06/04/2020] [Indexed: 10/24/2022] Open
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Aljaberi N, Ghulam E, Smitherman EA, Favier L, Dykes DMH, Danziger-Isakov LA, Brady RC, Huggins J. Maintaining Hepatitis B Protection in Immunocompromised Pediatric Rheumatology and Inflammatory Bowel Disease Patients. J Rheumatol 2020; 48:1314-1321. [PMID: 32739895 DOI: 10.3899/jrheum.200283] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/16/2020] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Hepatitis B virus (HBV) infection remains a significant public health challenge, particularly for immunocompromised patients. Our aim was to evaluate the serologic immunity in immunocompromised rheumatology and inflammatory bowel disease (IBD) patients, assess factors for serologic nonimmunity, and evaluate their response to 1 HBV booster dose. METHODS Immunocompromised rheumatology and IBD patients with completed HBV screening were identified. A chart review was performed to collect demographics, clinical information, baseline HBV serology results, and serologic response to booster vaccination. Serologic nonimmunity was defined as a negative/indeterminate hepatitis B surface antibody (anti-HBs) level. RESULTS Among 580 patients, 71% were nonimmune. The highest portion of nonimmune patients were 11-18 years old (P = 0.004). There was no significant difference between immune and nonimmune patients with regards to diagnosis (P = 0.34), age at diagnosis (P = 0.64), duration of treatment (P = 0.07), or type of medications (P = 0.08). Sixty-two percent of those who received a booster vaccine were rescreened, and most (68%) seroconverted. In those 18 years or older, only half seroconverted. CONCLUSION Results of this study support the benefit of HBV screening in immunosuppressed patients. Beginning at age 11 years, most patients lacked serologic immunity to HBV. Seroconversion for most patients 11-18 years occurred after 1 booster vaccine. Thus, for immunocompromised patients without recent HBV serologic data, obtaining the HBV serology beginning at age 11 years might be considered. Those 18 years and older were least likely to seroconvert after 1 booster, indicating that they may benefit from receiving the 3-dose HBV vaccine series.
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Affiliation(s)
- Najla Aljaberi
- N. Aljaberi, MBBS, MSc, J. Huggins, MD, Division of Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Ohio, USA;
| | - Enas Ghulam
- E. Ghulam, PhD, College of Sciences and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Emily A Smitherman
- E.A. Smitherman, MD, MSc, Division of Pediatric Rheumatology, University of Alabama at Birmingham, Alabama, USA
| | - Leslie Favier
- L. Favier, MD, MSc, Department of Pediatric Rheumatology, Children's Mercy, Kansas City, Missouri, USA
| | - Dana M H Dykes
- D.M. Dykes, MD, Department of Pediatric Gastroenterology, Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Lara A Danziger-Isakov
- L.A. Danziger-Isakov, MD, MPH, R.C. Brady, MD, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Ohio, USA
| | - Rebecca C Brady
- L.A. Danziger-Isakov, MD, MPH, R.C. Brady, MD, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Ohio, USA
| | - Jennifer Huggins
- N. Aljaberi, MBBS, MSc, J. Huggins, MD, Division of Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Ohio, USA
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Conrad A, Perry M, Langlois ME, Labussière-Wallet H, Barraco F, Ducastelle-Leprêtre S, Larcher MV, Balsat M, Boccard M, Chidiac C, Ferry T, Roure-Sobas C, Salles G, Valour F, Ader F. Efficacy and Safety of Revaccination against Tetanus, Diphtheria, Haemophilus influenzae Type b and Hepatitis B Virus in a Prospective Cohort of Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2020; 26:1729-1737. [PMID: 32428736 DOI: 10.1016/j.bbmt.2020.05.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 03/12/2020] [Accepted: 05/06/2020] [Indexed: 01/20/2023]
Abstract
Data on immunogenicity and safety of the recommended revaccination schedule against diphtheria, tetanus, poliomyelitis, pertussis, Haemophilus influenzae type b (Hib), and hepatitis B in adult allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients are limited. This prospective single-center cohort study (April 2014 to March 2018) included adult allo-HSCT recipients referred to a dedicated vaccinology consultation and vaccinated with the pediatric combined diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus, and Haemophilus influenzae type b (DTaP(±HB)-IPV-Hib) vaccine (3 doses 1 month apart, booster dose 1 year later). The proportion of responders to tetanus, diphtheria, Hib, and hepatitis B vaccine and geometric mean concentrations (GMCs) of antibodies were assessed before and up to 24 months after vaccination. A total of 106 patients were vaccinated at a median (interquartile range) time of 12.4 (10 to 18.4) months post-transplant. At 5.3 (4.8 to 6.6) and 23.1 (21.1 to 25.1) months after vaccine initiation, high and sustained rates of protective antibody titers were achieved for tetanus (97.8% [95% confidence interval (95% CI), 92.4% to 99.7%], n = 91/93 and 100% [95% CI, 92% to 100%], n = 44/44), diphtheria (94.6% [95% CI, 87.9% to 98.2%], n = 88/93 and 90.9% [95% CI, 78.3% to 97.5%], n = 40/44), Hib (96.6% [95% CI, 90.4% to 99.3%], n = 85/88 and 93% [95% CI, 80.9% to 98.5%], n = 40/43), and hepatitis B (83.5% [95% CI, 73.5% to 90.9%], n = 66/79 and 81.1% [95% CI, 64.8% to 92%], n = 30/37). Underlying disease, stem cell source, chronic graft-versus-host-disease, and extracorporeal photopheresis differentially influenced GMCs of tetanus, diphtheria, and hepatitis B antibodies after 3 doses but not in the long term (24 months). Six (5.7%) patients experienced mild side effects. The pediatric DTaP(±HB)-IPV-Hib vaccine was safe and effective in eliciting a sustained protective humoral response in adult allo-HSCT recipients. Hepatitis B revaccination might be optimized by using higher antigen doses.
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Affiliation(s)
- Anne Conrad
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Lyon, France; Université Claude Bernard Lyon I, Villeurbanne, France; Centre International de Recherche en Infectiologie, INSERM U1111, Université́ Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France.
| | - Marielle Perry
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Lyon, France
| | - Marie-Elodie Langlois
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Lyon, France; Université Claude Bernard Lyon I, Villeurbanne, France
| | - Hélène Labussière-Wallet
- Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie Clinique, Pierre-Bénite, France
| | - Fiorenza Barraco
- Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie Clinique, Pierre-Bénite, France
| | - Sophie Ducastelle-Leprêtre
- Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie Clinique, Pierre-Bénite, France
| | - Marie-Virginie Larcher
- Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie Clinique, Pierre-Bénite, France
| | - Marie Balsat
- Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie Clinique, Pierre-Bénite, France
| | - Mathilde Boccard
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Lyon, France; Centre International de Recherche en Infectiologie, INSERM U1111, Université́ Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France
| | - Christian Chidiac
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Lyon, France; Université Claude Bernard Lyon I, Villeurbanne, France
| | - Tristan Ferry
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Lyon, France; Université Claude Bernard Lyon I, Villeurbanne, France; Centre International de Recherche en Infectiologie, INSERM U1111, Université́ Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France
| | - Chantal Roure-Sobas
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Institut des Agents Infectieux, Lyon, France
| | - Gilles Salles
- Université Claude Bernard Lyon I, Villeurbanne, France; Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'Hématologie Clinique, Pierre-Bénite, France
| | - Florent Valour
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Lyon, France; Université Claude Bernard Lyon I, Villeurbanne, France; Centre International de Recherche en Infectiologie, INSERM U1111, Université́ Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France
| | - Florence Ader
- Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Service des Maladies Infectieuses et Tropicales, Lyon, France; Université Claude Bernard Lyon I, Villeurbanne, France; Centre International de Recherche en Infectiologie, INSERM U1111, Université́ Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France; INSERM, F-CRIN, Innovative Clinical Research Network in Vaccinology (I-REIVAC), Paris Cedex, France
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Edelman R, Deming ME, Toapanta FR, Heuser MD, Chrisley L, Barnes RS, Wasserman SS, Blackwelder WC, Handwerger BS, Pasetti M, Siddiqui KM, Sztein MB. The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route. Immun Ageing 2020; 17:9. [PMID: 32355503 PMCID: PMC7187507 DOI: 10.1186/s12979-020-00179-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 03/31/2020] [Indexed: 01/27/2023]
Abstract
BACKGROUND Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions. RESULTS Fifty-two healthy, community dwelling elderly adults (65-82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alum-adjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ≥10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21-34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%, p = 0.008). The low seroconversion rate in the IM group progressively declined with increasing age, and responders had significantly lower HBsAb titers and limited isotype responses. Moreover, T-CMI (proliferation and cytokine production) were significantly reduced in both percentage of responders and intensity of the response for both Th1 and Th2 subsets in the elderly. CONCLUSIONS Our data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B- and T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT04162223. Registered 14 November 2019. Retrospectively registered.
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Affiliation(s)
- Robert Edelman
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA
- Department of Medicine, University of Maryland School of Medicine, Baltimore, USA
| | - Meagan E. Deming
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA
- Department of Medicine, University of Maryland School of Medicine, Baltimore, USA
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, USA
| | - Franklin R. Toapanta
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA
- Department of Medicine, University of Maryland School of Medicine, Baltimore, USA
| | - Mark D. Heuser
- Department of Medicine, University of Maryland School of Medicine, Baltimore, USA
- Present Adress: Department of Veterans Affairs, Salisbury VA Health Care System, Salisbury, NC USA
| | - Lisa Chrisley
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA
| | - Robin S. Barnes
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA
| | - Steven S. Wasserman
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA
- Department of Medicine, University of Maryland School of Medicine, Baltimore, USA
- Present Adress: Office of Research, University of Virginia, Charlottesville, USA
| | - William C. Blackwelder
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, USA
| | - Barry S. Handwerger
- Rheumatology and Clinical Immunology, Dept of Medicine, University of Maryland School of Medicine, Baltimore, USA
| | - Marcela Pasetti
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, USA
- Department of Microbiology and Immunology, Dept of Medicine, University of Maryland School of Medicine, Baltimore, USA
| | - Khan M. Siddiqui
- Imaging Informatics and Body Magnetic Resonance Imaging unit, Veterans Affairs Maryland Health Care System Baltimore, Baltimore, MD USA
- Present Adress: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Marcelo B. Sztein
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA
- Department of Medicine, University of Maryland School of Medicine, Baltimore, USA
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, USA
- Department of Microbiology and Immunology, Dept of Medicine, University of Maryland School of Medicine, Baltimore, USA
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Abdoli A, Ardakani HM. Helminth infections and immunosenescence: The friend of my enemy. Exp Gerontol 2020; 133:110852. [PMID: 32007545 DOI: 10.1016/j.exger.2020.110852] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 12/13/2019] [Accepted: 01/21/2020] [Indexed: 12/14/2022]
Abstract
Age-associated alterations of the immune system, which known as "immunosenescence", is characterized by a decline in innate and adaptive immunity, which leading to increased susceptibility to age-associated diseases, such as infectious diseases, rheumatic disease and malignancies. On the other hand, helminth infections are among the most prevalent infections in older individuals, especially in the nursing homes. Most of helminth infections have minor clinical symptoms and usually causing chronic infections without treatment. Nevertheless, chronic helminthiasis alters immune responses somewhat similar to the immunosenescence. Some similarities also exist between helminth infections and immunosenescence: 1) both of them led to declining the immune responses; 2) undernutrition is a consequence of immunosenescence and helminthiasis; 3) vaccine efficacy declines in aging and individuals with helminth infections; 4) increase incidence and prevalence of infectious diseases in the elder individuals and patients with helminth infections; and 5) both of them promote tumorigenesis. Hence, it is probable that helminth infections in the elderly population can intensify the immunosenescence outcomes due to the synergistic immunoregulatory effects of each of them. It would be suggested that, diagnosis, treatment and prevention of helminth infections should be more considered in older individuals. Also, it would be suggested that helminths or their antigens can be used for investigation of immunosenescence because both of them possess some similarities in immune alterations. Taken together, this review offers new insights into the immunology of aging and helminth infections.
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Affiliation(s)
- Amir Abdoli
- Department of Parasitology and Mycology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran; Zoonoses Research Center, Jahrom University of Medical Sciences, Jahrom, Iran; Research Center for Noncommunicable Diseases, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.
| | - Hoda Mirzaian Ardakani
- Department of Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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Raven SFH, Hoebe CJPA, Vossen ACTM, Visser LG, Hautvast JLA, Roukens AHE, van Steenbergen JE. Serological response to three alternative series of hepatitis B revaccination (Fendrix, Twinrix, and HBVaxPro-40) in healthy non-responders: a multicentre, open-label, randomised, controlled, superiority trial. THE LANCET. INFECTIOUS DISEASES 2019; 20:92-101. [PMID: 31629649 DOI: 10.1016/s1473-3099(19)30417-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 07/02/2019] [Accepted: 07/12/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Serological non-response can be present after hepatitis B vaccination in healthy adults. We aimed to establish which of three revaccination regimens is most effective at inducing protective immunity METHODS: Healthy adults (aged 18-80 years) from 16 Dutch centres (13 public health services, two university hospitals, and one travel clinic) were included in this multicentre, parallel group, randomised, controlled, superiority trial. The inclusion criterion was vaccine non-response (hepatitis B surface antibody [anti-HBs] titre <10 IU/L) after a primary series with three doses of one type of recombinant vaccine against hepatitis B virus (either HBVaxPro-10 or Engerix-B at months 0, 1, and 6). Participants were individually randomly assigned (1:1:1:1) to a vaccination series of repeated initial vaccination (HBVaxPro 10 μg or Engerix-B 20 μg) as the control, or to Twinrix 20 μg, Fendrix 20 μg, or HBVaxPro 40 μg. We used a web-based randomisation programme, stratified by centre, with a block size of four. Participants and centres were unmasked to assignment after randomisation. Laboratory staff and investigators were masked to vaccine-group assignment. All revaccination schedules were identical, with intramuscular vaccinations at 0, 1, and 2 months. Anti-HBs was measured at 0, 1, 2, and 3 months. The primary outcome was the percentage of responders (anti-HBs titres ≥10 IU/L) at 3 months. Immunogenicity and safety analyses were based on an intention-to-vaccinate analysis, the immunogenicity analysis with last observation carried forward for missing data, and the Bonferroni and the Benjamini-Hochberg method were applied to correct for multiple testing. The trial was registered in the Dutch National Trial Register and inclusion has been stopped (identifier NL3011; EudraCT-number 2011-005627-40). FINDINGS The participants were recruited between Nov 1, 2012, and Sept 1, 2017. 480 participants were randomly assigned and included in intention-to-vaccinate analyses: 124 (26%) to control, 118 (25%) to Twinrix, 114 (24%) to HBVaxPro-40, and 124 (26%) to Fendrix. At month 3 the percentage of responders was 83 (67%) of 124 (95% CI 57·9-75·1 in the control group, 94 (80%) of the 118 (71·3-86·5) in the Twinrix group, 95 (83%) of 114 (75·2-89·7) in the HBVaxPro-40 group, and 108 (87%) of 124 (79·9-92·4) in the Fendrix group. Compared with the control group, the percentage of responders was superior for the HBVaxPro-40 group (adjusted difference 21·6% [95% CI 10·4-32·7], p=0·0204 [Bonferroni corrected p value]) and the Fendrix group (26·3% [15·4-37·3], p=0·0006), but not the Twinrix group (25·0% [13·0-37·0]; p=0·0846). One serious adverse event occurred (herpes zoster ophthalmicus) in the Fendrix group, which was not attributed to the vaccine. INTERPRETATION Revaccinating healthy non-responders with Fendrix or HBVaxPro-40 resulted in significantly higher proportions of responders and therefore indication for these vaccines should be expanded to enable revaccination of non-responders. FUNDING National Institute for Public Health and the Environment.
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Affiliation(s)
- Stijn F H Raven
- Department of Infectious Diseases, Regional Public Health Service West Brabant, Breda, Netherlands; Department of Medical Microbiology, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre, Maastricht, Netherlands.
| | - Christian J P A Hoebe
- Department of Medical Microbiology, Care and Public Health Research Institute (CAPHRI), Maastricht University Medical Centre, Maastricht, Netherlands; Department of Sexual Health, Infectious Diseases and Environmental Health, South Limburg Public Health Service, Netherlands
| | - Ann C T M Vossen
- Department of Medical Microbiology, Leiden University Medical Centre, Leiden, Netherlands
| | - Leo G Visser
- Department of Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands
| | - Jeannine L A Hautvast
- Department of Primary and Community Care, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands
| | - Anna H E Roukens
- Department of Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands
| | - Jim E van Steenbergen
- Department of Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, Netherlands
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Hyer RN, Janssen RS. Immunogenicity and safety of a 2-dose hepatitis B vaccine, HBsAg/CpG 1018, in persons with diabetes mellitus aged 60-70 years. Vaccine 2019; 37:5854-5861. [PMID: 31431412 DOI: 10.1016/j.vaccine.2019.08.005] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 08/06/2019] [Accepted: 08/07/2019] [Indexed: 01/01/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) remains a major public health issue, although it is a vaccine-preventable disease. Adults with diabetes are at greater risk of contracting HBV than the general population. Commonly used 3-dose HBV vaccines have reduced immunogenicity in older individuals and in those with diabetes mellitus. METHODS In this post hoc analysis of a phase 3 clinical trial, participants with type 2 diabetes mellitus aged 60-70 years received either 2-dose HBsAg/CpG 1018 (HEPLISAV-B®, n = 327) at 0 and 4 weeks and placebo at 24 weeks or 3-dose HBsAg/alum (Engerix-B®, n = 153) at 0, 4, and 24 weeks. Immunogenicity, including seroprotection rate (SPR) at week 28, and safety were assessed by subgroup (sex, body mass index, and smoking status). SPR was defined as antibody against hepatitis B surface antigen serum concentration ≥10 mIU/mL. RESULTS The SPR at week 28 was significantly higher with HBsAg/CpG 1018 (85.8% [235/274]) than with HBsAg/alum (58.5% [76/130]) in the per-protocol analysis, for an overall difference of 27.3% (95% CI, 18.0-36.8). SPRs with HBsAg/CpG 1018 were consistently markedly higher compared with HBsAg/alum, regardless of sex, body mass index, or smoking status. Adverse events and deaths were comparable between groups. CONCLUSIONS Two-dose HBsAg/CpG 1018 provides a higher level of seroprotection against HBV than does a 3-dose vaccine (HBsAg/alum) with a similar safety profile in patients aged 60-70 years with type 2 diabetes mellitus. Study identifier: NCT02117934.
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Affiliation(s)
- Randall N Hyer
- Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States.
| | - Robert S Janssen
- Dynavax Technologies Corporation, 2929 Seventh Street, Suite 100, Berkeley, CA 94710, United States.
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Kakisaka K, Sakai A, Yoshida Y, Miyasaka A, Takahashi F, Sumazaki R, Takikawa Y. Hepatitis B Surface Antibody Titers at One and Two Years after Hepatitis B Virus Vaccination in Healthy Young Japanese Adults. Intern Med 2019; 58:2349-2355. [PMID: 31118375 PMCID: PMC6746647 DOI: 10.2169/internalmedicine.2231-18] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Objective Since healthcare providers face an increased risk of hepatitis B virus (HBV) infection because of their work, vaccination plays a critical role in preventing HBV transmission. However, the duration for which acquired HBV surface antibodies (anti-HBs) persist remains unknown. To evaluate the primary immunologic response to HBV vaccination and its persistence in healthy Japanese adolescents. Methods In total, 690 young adults underwent HBV vaccination with a three-dose schedule. The primary response was determined by the anti-HBs titers at 1-2 months after the final dosage. Subjects with anti-HBs titers of <10, 10-100, and >100 mIU/mL were classified as "non-responders," "low-responders," and "sufficient responders," respectively. Anti-HB titers were re-measured at 1 or 2 years after vaccination. Results First, 95.8% and 72.8% of the subjects had anti-HBs titers of >10 and >100 mIU/mL, respectively, as a primary response. The anti-HBs titers measured at 1 and 2 years after vaccination were significantly correlated with those of the primary response (1 year: r=0.893, p<0.0001; 2 years: r=0.902, p<0.001). Most subjects with a titer of >100 mIU/mL at the primary response maintained an anti-HBs titer of >10 mIU/mL [1 year after vaccination, 208/209 (99.5%); 2 years after vaccination, 72/81 (90.1%)]. However, in subjects with a primary response of 10-100 mIU/mL the anti-HBs titer frequently declined; 17/38 (44.7%) and 9/10 (90.0%) subjects had a titer of <10 mIU/mL at 1 and 2 years, respectively. Conclusion The primary response was associated with the anti-HBs titers at 1 and 2 years after vaccination, and the anti-HBs titers of 54.2% of the low responders were not maintained for 2 years, even if they were vaccinated as healthy young adults.
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Affiliation(s)
- Keisuke Kakisaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
| | - Aiko Sakai
- Department of Child Health, Faculty of Medicine, Tsukuba University, Japan
| | - Yuichi Yoshida
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
| | - Akio Miyasaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
| | - Fumiaki Takahashi
- Division of Medical Engineering, Department of Information Science, Iwate Medical University, Japan
| | - Ryo Sumazaki
- Department of Child Health, Faculty of Medicine, Tsukuba University, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
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Expression and detection of anti-HBs antibodies after hepatitis B virus infection or vaccination in the context of protective immunity. Arch Virol 2019; 164:2645-2658. [DOI: 10.1007/s00705-019-04369-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 07/04/2019] [Indexed: 12/14/2022]
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Pratt PK, Nunes D, Long MT, Farraye FA. Improved Antibody Response to Three Additional Hepatitis B Vaccine Doses Following Primary Vaccination Failure in Patients with Inflammatory Bowel Disease. Dig Dis Sci 2019; 64:2031-2038. [PMID: 30945037 PMCID: PMC6764090 DOI: 10.1007/s10620-019-05595-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 03/18/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Studies have shown the efficacy of hepatitis B (HBV) vaccination in patients with inflammatory bowel disease (IBD) is impaired, but few data exist regarding the effectiveness of revaccination strategies following primary vaccination failure. Our aim was to analyze the association between administration of additional vaccine doses and hepatitis B surface antibody (HBsAb) seroconversion. METHODS This is a retrospective cohort study. Inclusion criteria are as follows: age ≥ 18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), inadequate HBsAb < 10 IU/L following initial HBV vaccination series, subsequent administration of 1-3 additional doses of HBV vaccine with follow-up serum HBsAb measurements. Patients were stratified into groups of ≤ 2 or 3 doses received. Primary outcome was achieving HBsAb > 10 IU/L. Outcomes were stratified by age ≥ or < 40 years. We performed logistic and linear multivariable regression analyses for categorical and continuous data. RESULTS The study cohort consists of (n = 149) 54.4% women; 77.9% white; 72.6% with CD, with mean age: 46.2. Patients of all ages and age ≥ 40 years, who received 3 additional doses of vaccine, were more likely to achieve seroprotective HBsAb levels than patients who received 1 or 2 doses (OR 1.77, P = 0.01; OR 1.9, P = 0.03, respectively, after adjusting for age, sex, race, immunosuppressive medication exposure, time between vaccine/titer). CONCLUSIONS Following initial HBV vaccination failure, patients with IBD of all ages are more likely to develop seroprotective levels of HBsAb following 3 additional vaccine doses, rather than 1 or 2 alone. In patients who fail primary HBV vaccination, providers should consider a more aggressive revaccination strategy with an additional 3-dose series.
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Affiliation(s)
- Perry K. Pratt
- Present Address: Division of Gastroenterology and Hepatology, University of Connecticut Health, Farmington, CT, USA
| | - David Nunes
- Section of Gastroenterology, Boston University Medical Center, 85 East Concord Street, Boston, MA 02118, USA
| | - Michelle T. Long
- Section of Gastroenterology, Boston University Medical Center, 85 East Concord Street, Boston, MA 02118, USA
| | - Francis A. Farraye
- Section of Gastroenterology, Boston University Medical Center, 85 East Concord Street, Boston, MA 02118, USA
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Dimitrov Y, Ducher M, Kribs M, Laurent G, Richter S, Fauvel JP. Variables linked to hepatitis B vaccination success in non-dialyzed chronic kidney disease patients: Use of a bayesian model. Nephrol Ther 2019; 15:215-219. [PMID: 31129001 DOI: 10.1016/j.nephro.2019.02.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 02/01/2019] [Accepted: 02/03/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatitis B vaccination is recommended for chronic kidney disease (CKD) patients before starting dialysis. We performed an analyis aimed to describe the clinical and biological parameters related to the success of vaccination in CKD patients before starting dialysis. METHODS We extracted data of 170 non-dialyzed patients who were offered hepatitis B vaccination from a register. They received a first vaccination of 40μg followed by boosters after one, two and six months. Patients were considered protected if their hepatitis B antibody level was >10IU/L, three months apart. A logistic regression and a Bayesian model were used to describe the relationships between variables and the success of vaccination. RESULTS Vaccination protected 50.6% of the patients. Model adjustment to the data was higher using the Bayesian model compared to the logistic regression (with area under the ROC curve of 0.955±0.007 vs 0.775±0.066 respectively). The Bayesian model's robustness studied using a 10 fold cross validation showed a percentage of misclassified subjects of 12.4±1.8%, a sensitivity of 87.7±0.3%, a specificity of 87.5±0.3%, a positive predictive value of 87.8±0.3% and negative predictive value of 87.4±0.2%. As classified by the Bayesian model, the variables most related to successful vaccination were, in descending order: age, eGFR, protidemia, albuminemia, cause of renal failure, gender, previous vaccination and weight. CONCLUSION The Bayesian network confirmed that both kidney function and nutritional status of patients are important factors to explain the success of vaccination against hepatitis B in CKD patients before dialysis. For research purposes, before an external validation, the network can be used online at www.hed.cc/?s=Bhepatitis&n=ReseauhepatiteBsup10.neta.
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Affiliation(s)
- Yves Dimitrov
- Nephrology Department, centre hospitalier de Haguenau, 64, avenue du professeur Leriche, 67500 Haguenau, France.
| | - Michel Ducher
- Pharmacy Department, hospices civils de Lyon, université Claude-Bernard Lyon 1, 69000 Lyon, France
| | - Marc Kribs
- Nephrology Department, centre hospitalier de Haguenau, 64, avenue du professeur Leriche, 67500 Haguenau, France
| | - Guillaume Laurent
- Nephrology Department, centre hospitalier de Haguenau, 64, avenue du professeur Leriche, 67500 Haguenau, France
| | | | - Jean-Pierre Fauvel
- Hospices civils de Lyon, université Claude-Bernard Lyon 1, 69000 Lyon, France
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Laksananun N, Praparattanapan J, Kotarathititum W, Supparatpinyo K, Chaiwarith R. Immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody. AIDS Res Ther 2019; 16:10. [PMID: 31053142 PMCID: PMC6498566 DOI: 10.1186/s12981-019-0225-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 04/10/2019] [Indexed: 12/15/2022] Open
Abstract
Background Presence of isolated anti-HBc antibody is common in HIV-infected patients in endemic areas and could be caused by prior HBV infection with loss of anti-HBs antibody. The role of vaccination in these patients remains controversial and is based largely on limited and low quality data. We, therefore, conducted this study to determine immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody. Methods An open-label, randomized controlled trial was conducted among HIV-infected patients visiting HIV clinic of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand between July and September 2017. Inclusion criteria included ≥ 18 years of age, currently on a stable antiretroviral regimen, CD4+ cell count ≥ 200 cells/mm3, plasma HIV-1 RNA < 20 copies/mL, and isolated anti-HBc antibody. The participants were randomized to receive either 3 standard doses (20 µg at month 0, 1, 6) or 4 standard-doses (20 µg at month 0, 1, 2, 6) of IM HBV vaccination, and were evaluated for anamnestic response at week 4 and vaccine response at week 28. Results Of the 97 patients screened, 54 (32 male, mean age of 46 years) were enrolled and 27 were allocated to each of the vaccination groups. Anamnestic response occurred in 25.9% vs. 33.3% in 3-dose group vs. 4-dose group, respectively (p = 0.551). The vaccine response rates at week 28 were 85.2% in 3-dose group vs. 88.9% in 4-dose group (p = 1.000); geometric mean titer of anti-HBs antibody at week 28 was 63.8 and 209.8 mIU/mL in 3-dose group and 4-dose group, respectively (p = 0.030). No adverse events were reported. Conclusions An anamnestic response occurred in one-third of Thai HIV-infected patients with isolated anti-HBc antibody who received one dose of HBV vaccination; however, the majority were still unprotected. The use of either 3 or 4 standard-doses of vaccination was highly effective and should be recommended in all HIV-infected individuals with isolated anti-HBc antibody. Trial registration ClinicalTrials.gov; NCT03212911. Registered 11 July 2019, https://clinicaltrials.gov/ct2/show/NCT03212911 Electronic supplementary material The online version of this article (10.1186/s12981-019-0225-3) contains supplementary material, which is available to authorized users.
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Sulfated archaeol glycolipids: Comparison with other immunological adjuvants in mice. PLoS One 2018; 13:e0208067. [PMID: 30513093 PMCID: PMC6279041 DOI: 10.1371/journal.pone.0208067] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 11/12/2018] [Indexed: 12/24/2022] Open
Abstract
Archaeosomes are liposomes traditionally comprised of total polar lipids (TPL) or semi-synthetic glycerolipids of ether-linked isoprenoid phytanyl cores with varied glyco- and amino-head groups. As adjuvants, they induce robust, long-lasting humoral and cell-mediated immune responses and enhance protection in murine models of infectious disease and cancer. Traditional total polar lipid (TPL) archaeosome formulations are relatively complex and first generation semi-synthetic archaeosomes involve many synthetic steps to arrive at the final desired glycolipid composition. We have developed a novel archaeosome formulation comprising a sulfated disaccharide group covalently linked to the free sn-1 hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA) that can be more readily synthesized yet retains strong immunostimulatory activity for induction of cell-mediated immunity following systemic immunization. Herein, we have evaluated the immunostimulatory effects of SLA archaeosomes when used as adjuvant with ovalbumin (OVA) and hepatitis B surface antigen (HBsAg) and compared this to various other adjuvants including TLR3/4/9 agonists, oil-in-water and water-in-oil emulsions and aluminum hydroxide. Overall, we found that semi-synthetic sulfated glycolipid archaeosomes induce strong Ag-specific IgG titers and CD8 T cells to both antigens. In addition, they induce the expression of a number of cytokines/chemokines including IL-6, G-CSF, KC & MIP-2. SLA archaeosome formulations demonstrated strong adjuvant activity, superior to many of the other tested adjuvants.
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Chang JY, Jung SA, Moon CM, Kim SE, Jung HK, Shim KN. Response to hepatitis B vaccination in patients with inflammatory bowel disease: a prospective observational study in Korea. Intest Res 2018; 16:599-608. [PMID: 30301330 PMCID: PMC6223458 DOI: 10.5217/ir.2018.00012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 05/25/2018] [Indexed: 02/04/2023] Open
Abstract
Background/Aims Testing for hepatitis B virus (HBV) serologic markers and appropriate vaccination are required in the management of inflammatory bowel disease (IBD) patients. We evaluated immunogenicity for HBV in IBD patients and the response to the HBV vaccination. Methods From May 2014 to August 2016, patients diagnosed with IBD were prospectively included and evaluated for antibody to hepatitis B surface antigen, antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen. Among the 73 patients who were confirmed with nonimmunity to HBV, 44 patients who had completed the 3-dose HBV vaccination series received a single booster vaccination, while 29 patients who had not completed the vaccinations series or were unsure of receiving the vaccination received a full vaccination series. Results An optimal response was obtained in 70.5% of the patients in the booster group, and 89.7% of the patients in the full vaccination group. Age younger than 26 years (odds ratio [OR], 6.01; 95% confidence interval [CI], 1.15–31.32; P=0.033) and a complete previous vaccination series (OR, 0.15; 95% CI, 0.03–0.80; P=0.026) were associated with optimal vaccine response. Previous complete vaccination series (OR, 0.11; 95% CI, 0.02–0.73; P=0.022) was the only predictive factor for lower compliance. Conclusions The response to the HBV vaccination was lower in patients older than 26 years and for those patients with a complete vaccination history. Since patients with a complete vaccination history also had poor compliance, serum HBV-titers should be checked more thoroughly, and a full vaccination series should be administered in cases when there is a negative response to the booster vaccination.
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Affiliation(s)
- Ji Young Chang
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Sung-Ae Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Chang Mo Moon
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Seong-Eun Kim
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Ki-Nam Shim
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
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Reed SG, Carter D, Casper C, Duthie MS, Fox CB. Correlates of GLA family adjuvants' activities. Semin Immunol 2018; 39:22-29. [PMID: 30366662 PMCID: PMC6289613 DOI: 10.1016/j.smim.2018.10.004] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 10/03/2018] [Indexed: 12/30/2022]
Abstract
Lipopolysaccharide (LPS) is a well-defined agonist of Toll-like receptor (TLR) 4 that activates innate immune responses and influences the development of the adaptive response during infection with Gram-negative bacteria. Many years ago, Dr. Edgar Ribi separated the adjuvant activity of LPS from its toxic effects, an effort that led to the development of monophosphoryl lipid A (MPL). MPL, derived from Salmonella minnesota R595, has progressed through clinical development and is now used in various product-enabling formulations to support the generation of antigen-specific responses in several commercial and preclinical vaccines. We have generated several synthetic lipid A molecules, foremost glucopyranosyl lipid adjuvant (GLA) and second-generation lipid adjuvant (SLA), and have advanced these to clinical trial for various indications. In this review we summarize the potential and current positioning of TLR4-based adjuvant formulations in approved and emerging vaccines.
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Affiliation(s)
- Steven G Reed
- Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102 USA.
| | - Darrick Carter
- Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102 USA.
| | - Corey Casper
- Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102 USA.
| | - Malcolm S Duthie
- Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102 USA.
| | - Christopher B Fox
- Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102 USA.
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Wang L, Cao D, Wang L, Zhao J, Nguyen LN, Dang X, Ji Y, Wu XY, Morrison ZD, Xie Q, El Gazzar M, Ning S, Moorman JP, Yao ZQ. HCV-associated exosomes promote myeloid-derived suppressor cell expansion via inhibiting miR-124 to regulate T follicular cell differentiation and function. Cell Discov 2018; 4:51. [PMID: 30210805 PMCID: PMC6131392 DOI: 10.1038/s41421-018-0052-z] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 06/14/2018] [Accepted: 06/19/2018] [Indexed: 12/16/2022] Open
Abstract
Virus-infected cells can regulate non-permissive bystander cells, but the precise mechanisms remain incompletely understood. Here we report that this process can be mediated by transfer of viral RNA-loaded exosomes shed from infected cells to myeloid-derived suppressor cells (MDSCs), which in turn regulate the differentiation and function of T cells during viral infection. Specifically, we demonstrated that patients with chronic hepatitis C virus (HCV) infection exhibited significant increases in T follicular regulatory (TFR) cells and decreases in T follicular helper (TFH) cells. These MDSC-mediated T-cell dysregulations resulted in an increased ratio of TFR/TFH and IL-10 production in peripheral blood. Specifically, co-culture of MDSCs derived from HCV patients with healthy peripheral blood mononuclear cells (PBMCs) induced expansion of TFR, whereas depletion of MDSCs from PBMCs of HCV patients reduced the increases in TFR frequency and IL-10 production, and promoted the differentiation of IFN-γ-producing TFH cells. Importantly, we found that exosomes isolated from the plasma of HCV patients and supernatant of HCV-infected hepatocytes could drive monocytic myeloid cell differentiation into MDSCs. These exosomes were enriched in tetraspanins, such as CD63 and CD81, and contained HCV RNA, but exosomes isolated from patients with antiviral treatment contained no HCV RNA and could not induce MDSC differentiation. Notably, these HCV RNA-containing exosomes (HCV-Exo) were sufficient to induce MDSCs. Furthermore, incubation of healthy myeloid cells with these HCV-Exo inhibited the expression of miR-124, whereas reconstitution of PBMCs with miR-124 abolished the effects of HCV-Exo on MDSC induction. Taken together, these results indicate that HCV-associated exosomes can transfer immunomodulatory viral RNA from infected cells to neighboring immune cells and trigger MDSC expansion, which subsequently promotes TFR differentiation and inhibits TFH function. This study reveals a previously unrecognized path that represents a novel mechanism of immune dysregulation during chronic viral infection.
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Affiliation(s)
- Lin Wang
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
- Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015 China
| | - Dechao Cao
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
| | - Ling Wang
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
| | - Juan Zhao
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
| | - Lam Nhat Nguyen
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
| | - Xindi Dang
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
| | - Yingjie Ji
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
- Center of Cadre Health Care, Beijing 302 Hospital, Beijing, 100000 China
| | - Xiao Y. Wu
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
| | - Zheng D. Morrison
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
| | - Qian Xie
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
| | - Mohamed El Gazzar
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
| | - Shunbin Ning
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
| | - Jonathan P. Moorman
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
- Hepatitis (HCV/HIV) Program, James H. Quillen VA Medical Center, Department of Veterans Affairs, Johnson City, TN 37614 USA
| | - Zhi Q. Yao
- Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 USA
- Division of Infectious, Inflammatory and Immunologic Diseases, Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN 37614 USA
- Hepatitis (HCV/HIV) Program, James H. Quillen VA Medical Center, Department of Veterans Affairs, Johnson City, TN 37614 USA
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Improved CD4 T cell profile in HIV-infected subjects on maraviroc-containing therapy is associated with better responsiveness to HBV vaccination. J Transl Med 2018; 16:238. [PMID: 30157873 PMCID: PMC6116502 DOI: 10.1186/s12967-018-1617-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 08/23/2018] [Indexed: 12/30/2022] Open
Abstract
Background Maraviroc-containing combined antiretroviral therapy (MVC-cART) improved the response to the hepatitis B virus (HBV) vaccine in HIV-infected subjects younger than 50 years old. We aimed here to explore the effect of this antiretroviral therapy on different immunological parameters that could account for this effect. Methods We analysed baseline samples of vaccinated subjects under 50 years old (n = 41). We characterized the maturational subsets and the expression of activation, senescence and prone-to-apoptosis markers on CD4 T-cells; we also quantified T-regulatory cells (Treg) and dendritic cell (DC) subsets. We used binary logistic regression to evaluate the immunological impact of MVC-cART, correlation with MVC exposure and linear regression for association with the magnitude of the HBV vaccine response. Results HIV-infected subjects on MVC-cART prior to vaccination showed increased recent thymic emigrants levels and reduced myeloid-DC levels. A longer exposure to MVC-cART was associated with lower frequencies of Tregs and activated and proliferating CD4 T-cells. Furthermore, the frequencies of activated and proliferating CD4 T-cells were inversely associated with the magnitude of the HBV vaccine response. Conclusion The beneficial effect of MVC-cART in the HBV vaccine response in subjects below 50 years old could be partially mediated by its reducing effect on the frequencies of activated and proliferating CD4 T-cells prior to vaccination. Electronic supplementary material The online version of this article (10.1186/s12967-018-1617-1) contains supplementary material, which is available to authorized users.
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Sekiba K, Otsuka M, Ohno M, Yamagami M, Kishikawa T, Suzuki T, Ishibashi R, Seimiya T, Tanaka E, Koike K. Hepatitis B virus pathogenesis: Fresh insights into hepatitis B virus RNA. World J Gastroenterol 2018; 24:2261-2268. [PMID: 29881235 PMCID: PMC5989240 DOI: 10.3748/wjg.v24.i21.2261] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 04/24/2018] [Accepted: 04/26/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is still a worldwide health concern. While divergent factors are involved in its pathogenesis, it is now clear that HBV RNAs, principally templates for viral proteins and viral DNAs, have diverse biological functions involved in HBV pathogenesis. These functions include viral replication, hepatic fibrosis and hepatocarcinogenesis. Depending on the sequence similarities, HBV RNAs may act as sponges for host miRNAs and may deregulate miRNA functions, possibly leading to pathological consequences. Some parts of the HBV RNA molecule may function as viral-derived miRNA, which regulates viral replication. HBV DNA can integrate into the host genomic DNA and produce novel viral-host fusion RNA, which may have pathological functions. To date, elimination of HBV-derived covalently closed circular DNA has not been achieved. However, RNA transcription silencing may be an alternative practical approach to treat HBV-induced pathogenesis. A full understanding of HBV RNA transcription and the biological functions of HBV RNA may open a new avenue for the development of novel HBV therapeutics.
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Affiliation(s)
- Kazuma Sekiba
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Motoko Ohno
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Mari Yamagami
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Takahiro Kishikawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Tatsunori Suzuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Rei Ishibashi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Takahiro Seimiya
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Eri Tanaka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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Weinberger B, Haks MC, de Paus RA, Ottenhoff THM, Bauer T, Grubeck-Loebenstein B. Impaired Immune Response to Primary but Not to Booster Vaccination Against Hepatitis B in Older Adults. Front Immunol 2018; 9:1035. [PMID: 29868000 PMCID: PMC5962691 DOI: 10.3389/fimmu.2018.01035] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 04/25/2018] [Indexed: 12/12/2022] Open
Abstract
Many current vaccines are less immunogenic and less effective in elderly compared to younger adults due to age-related changes of the immune system. Most vaccines utilized in the elderly contain antigens, which the target population has had previous contact with due to previous vaccination or infection. Therefore, most studies investigating vaccine-induced immune responses in the elderly do not analyze responses to neo-antigens but rather booster responses. However, age-related differences in the immune response could differentially affect primary versus recall responses. We therefore investigated the impact of age on primary and recall antibody responses following hepatitis B vaccination in young and older adults. Focused gene expression profiling was performed before and 1 day after the vaccination in order to identify gene signatures predicting antibody responses. Young (20-40 years; n = 24) and elderly (>60 years; n = 17) healthy volunteers received either a primary series (no prior vaccination) or a single booster shot (documented primary vaccination more than 10 years ago). Antibody titers were determined at days 0, 7, and 28, as well as 6 months after the vaccination. After primary vaccination, antibody responses were lower and delayed in the elderly compared to young adults. Non-responders after the three-dose primary series were only observed in the elderly group. Maximum antibody concentrations after booster vaccination were similar in both age groups. Focused gene expression profiling identified 29 transcripts that correlated with age at baseline and clustered in a network centered around type I interferons and pro-inflammatory cytokines. In addition, smaller 8- and 6-gene signatures were identified at baseline that associated with vaccine responsiveness during primary and booster vaccination, respectively. When evaluating the kinetic changes in gene expression profiles before and after primary vaccination, a 33-gene signature, dominated by IFN-signaling, pro-inflammatory cytokines, inflammasome components, and immune cell subset markers, was uncovered that was associated with vaccine responsiveness. By contrast, no such transcripts were identified during booster vaccination. Our results document that primary differs from booster vaccination in old age, in regard to antibody responses as well as at the level of gene signatures. Clinical Trial Registration www.clinicaltrialsregister.eu, this trial was registered at the EU Clinical Trial Register (EU-CTR) with the EUDRACT-Nr. 2013-002589-38.
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Affiliation(s)
- Birgit Weinberger
- Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria
| | - Mariëlle C Haks
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
| | - Roelof A de Paus
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
| | - Tom H M Ottenhoff
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands
| | - Tanja Bauer
- Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany
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Efficacy of Hepatitis B Vaccination in Under Five-Year-Old Children in Iran: A Systematic Review and Meta-Analysis Study. HEPATITIS MONTHLY 2018. [DOI: 10.5812/hepatmon.65385] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Li X, Xu Y, Dong Y, Yang X, Ye B, Wang Y, Chen Y. Monitoring the efficacy of infant hepatitis B vaccination and revaccination in 0- to 8-year-old children: Protective anti-HBs levels and cellular immune responses. Vaccine 2018; 36:2442-2449. [PMID: 29588118 DOI: 10.1016/j.vaccine.2018.03.044] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 03/02/2018] [Accepted: 03/15/2018] [Indexed: 01/16/2023]
Abstract
Vaccination against hepatitis B virus (HBV) is recommended worldwide. The aim of this study was to assess the efficacy of infant hepatitis B vaccination and revaccination in 0- to 8-year-old children in the context of protective anti-HBs levels and cellular immune responses. Using a random questionnaire survey, 1695 pre-school children were recruited as research subjects during January 2015 to June 2017. Blood samples were obtained to measure HBV serological markers as well as peripheral immunocytes. The children were divided into non-, low- and hyper- responsive groups (NR, LR, and HR) based on the vaccination efficacy. Additionally, the effect of revaccination on the NR group was evaluated at 1 month after completion of the vaccination course. Among a total of 1695 children, 1591 (93.86%) were infants who were followed while undergoing their primary course of hepatitis B vaccination at the 0-1-6 month schedule, and 1249 (79.30%) of them developed antibodies against HBsAg (anti-HBs) titers greater than 10 IU/L. The results of immunocyte studies indicated that the CD8+ T cells, CD4+CD45RO+ T cells, CD8+CD45RA+ T cells, and T follicular helper (Tfh) cells increased significantly in NR compared with HR. However, lymphocytes, CD4+ T cells, and CD4+CD45RA+ T cells in NR were lower than that in HR. 96 of the non-response cases showed seroprotection after revaccination among 103 cases. Therefore, most of the preschool children who received hepatitis B vaccine in infancy achieved significant seroprotection. Seroconversion rates of individuals revaccinated after initial vaccination failure were significantly higher than those after primary vaccination. Different vaccination efficacy groups showed significant changes in circulating immunocytes, which might be a factor affecting the recombinant HBV vaccine's immune effectiveness.
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Affiliation(s)
- Xuefen Li
- Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China
| | - Yumiao Xu
- Clinical Laboratory, Maternal and Child Health Care of Family Planning Service Center of Lin'an, Lin'an Zhejiang, China
| | - Yuejiao Dong
- Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China
| | - Xianzhi Yang
- Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China
| | - Bo Ye
- Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China
| | - Yiyin Wang
- Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China
| | - Yu Chen
- Department of Laboratory Medicine, Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79(#) Qingchun Road, Hangzhou 310003, China.
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