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Tulaeva I, Lehmann F, Goldmann N, Dubovets A, Trifonova D, Tulaev M, Cornelius C, Weber M, Focke-Tejkl M, Karaulov A, Henning R, Springer DN, Wiedermann U, Glebe D, Valenta R. The PreS-Based Recombinant Vaccine VVX001 Induces Hepatitis B Virus Neutralizing Antibodies in a Low-Responder to HBsAg-Based HBV Vaccines. Vaccines (Basel) 2024; 12:1123. [PMID: 39460290 PMCID: PMC11511130 DOI: 10.3390/vaccines12101123] [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: 07/23/2024] [Revised: 09/20/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Background: Approximately 10-20% of subjects vaccinated with HBsAg-based hepatitis B virus (HBV) vaccines are non-responders. BM32 is a recombinant grass pollen allergy vaccine containing the HBV-derived preS surface antigen as an immunological carrier protein. PreS includes the binding site of HBV to its receptor on hepatocytes. We investigated whether immunological non-responsiveness to HBV after repeated HBsAg-based vaccinations could be overcome by immunization with VVX001 (i.e., alum-adsorbed BM325, a component of BM32). Methods: A subject failing to develop protective HBV-specific immunity after HBsAg-based vaccination received five monthly injections of 20 µg VVX001. PreS-specific antibody responses were measured by enzyme-linked immunosorbent assay (ELISA) and micro-array technology. Serum reactivity to subviral particles of different HBV genotypes was determined by sandwich ELISA. PreS-specific T cell responses were monitored by carboxyfluorescein diacetate succinimidyl ester (CFSE) staining and subsequent flow cytometry. HBV neutralization was assessed using cultured HBV-infected HepG2 cells. Results: Vaccination with VVX001 induced a strong and sustained preS-specific antibody response composed mainly of the IgG1 subclass. PreS-specific IgG antibodies were primarily directed to the N-terminal part of preS containing the sodium taurocholate co-transporting polypeptide (NTCP) attachment site. IgG reactivity to subviral particles as well as to the N-terminal preS-derived peptides was comparable for HBV genotypes A-H. A pronounced reactivity of CD3+CD4+ lymphocytes specific for preS after the complete injection course remaining up to one year after the last injection was found. Maximal HBV neutralization (98.4%) in vitro was achieved 1 month after the last injection, which correlated with the maximal IgG reactivity to the N-terminal part of preS. Conclusions: Our data suggest that VVX001 may be used as a preventive vaccination against HBV even in non-responders to HBsAg-based HBV vaccines.
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Affiliation(s)
- Inna Tulaeva
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; (I.T.)
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia
| | - Felix Lehmann
- Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, German Center for Infection Research (DZIF), Partner Site Giessen-Marburg Langen, Justus Liebig University, 35390 Giessen, Germany; (F.L.)
| | - Nora Goldmann
- Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, German Center for Infection Research (DZIF), Partner Site Giessen-Marburg Langen, Justus Liebig University, 35390 Giessen, Germany; (F.L.)
| | - Alexandra Dubovets
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia
| | - Daria Trifonova
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; (I.T.)
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia
| | - Mikhail Tulaev
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; (I.T.)
| | - Carolin Cornelius
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; (I.T.)
| | - Milena Weber
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; (I.T.)
| | - Margarete Focke-Tejkl
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; (I.T.)
| | - Alexander Karaulov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia
| | | | | | - Ursula Wiedermann
- Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
| | - Dieter Glebe
- Institute of Medical Virology, National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, German Center for Infection Research (DZIF), Partner Site Giessen-Marburg Langen, Justus Liebig University, 35390 Giessen, Germany; (F.L.)
| | - Rudolf Valenta
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria; (I.T.)
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia
- NRC Institute of Immunology FMBA of Russia, 115552 Moscow, Russia
- Karl Landsteiner University of Health Sciences, 3500 Krems, Austria
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Choi Y, Lee GS, Li S, Lee JW, Mixson-Hayden T, Woo J, Xia D, Prausnitz MR, Kamili S, Purdy MA, Tohme RA. Hepatitis B vaccine delivered by microneedle patch: Immunogenicity in mice and rhesus macaques. Vaccine 2023; 41:3663-3672. [PMID: 37179166 PMCID: PMC10961677 DOI: 10.1016/j.vaccine.2023.05.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 04/17/2023] [Accepted: 05/01/2023] [Indexed: 05/15/2023]
Abstract
Vaccination against hepatitis B using a dissolving microneedle patch (dMNP) could increase access to the birth dose by reducing expertise needed for vaccine administration, refrigerated storage, and safe disposal of biohazardous sharps waste. In this study, we developed a dMNP to administer hepatitis B surface antigen (HBsAg) adjuvant-free monovalent vaccine (AFV) at doses of 5 µg, 10 µg, and 20 µg, and compared its immunogenicity to vaccination with 10 µg of standard monovalent HBsAg delivered by intramuscular (IM) injection either in an AFV format or as aluminum-adjuvanted vaccine (AAV). Vaccination was performed on a three dose schedule of 0, 3, and 9 weeks in mice and 0, 4, and 24 weeks in rhesus macaques. Vaccination by dMNP induced protective levels of anti-HBs antibody responses (≥10 mIU/ml) in mice and rhesus macaques at all three HBsAg doses studied. HBsAg delivered by dMNP induced higher anti-HBsAg antibody (anti-HBs) responses than the 10 µg IM AFV, but lower responses than 10 µg IM AAV, in mice and rhesus macaques. HBsAg-specific CD4+ and CD8+ T cell responses were detected in all vaccine groups. Furthermore, we analyzed differential gene expression profiles related to each vaccine delivery group and found that tissue stress, T cell receptor signaling, and NFκB signaling pathways were activated in all groups. These results suggest that HBsAg delivered by dMNP, IM AFV, and IM AAV have similar signaling pathways to induce innate and adaptive immune responses. We further demonstrated that dMNP was stable at room temperature (20 °C-25 °C) for 6 months, maintaining 67 ± 6 % HBsAg potency. This study provides evidence that delivery of 10 µg (birth dose) AFV by dMNP induced protective levels of antibody responses in mice and rhesus macaques. The dMNPs developed in this study could be used to improve hepatitis B birth dose vaccination coverage levels in resource limited regions to achieve and maintain hepatitis B elimination.
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Affiliation(s)
- Youkyung Choi
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, US Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
| | - Grace Sanghee Lee
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, US Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
| | - Song Li
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
| | - Jeong Woo Lee
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
| | - Tonya Mixson-Hayden
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, US Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
| | - Jungreem Woo
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, US Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
| | - Dengning Xia
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
| | - Mark R Prausnitz
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
| | - Saleem Kamili
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, US Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
| | - Michael A Purdy
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD and TB Prevention, US Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
| | - Rania A Tohme
- Global Immunization Division, Centers for Global Health, CDC, Atlanta, GA, USA.
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Ouyang J, Zaongo SD, Zhang X, Qi M, Hu A, Wu H, Chen Y. Microbiota-Meditated Immunity Abnormalities Facilitate Hepatitis B Virus Co-Infection in People Living With HIV: A Review. Front Immunol 2022; 12:755890. [PMID: 35069530 PMCID: PMC8770824 DOI: 10.3389/fimmu.2021.755890] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 12/17/2021] [Indexed: 12/12/2022] Open
Abstract
Hepatitis B virus (HBV) co-infection is fairly common in people living with HIV (PLWH) and affects millions of people worldwide. Identical transmission routes and HIV-induced immune suppression have been assumed to be the main factors contributing to this phenomenon. Moreover, convergent evidence has shown that people co-infected with HIV and HBV are more likely to have long-term serious medical problems, suffer more from liver-related diseases, and have higher mortality rates, compared to individuals infected exclusively by either HIV or HBV. However, the precise mechanisms underlying the comorbid infection of HIV and HBV have not been fully elucidated. In recent times, the human gastrointestinal microbiome is progressively being recognized as playing a pivotal role in modulating immune function, and is likely to also contribute significantly to critical processes involving systemic inflammation. Both antiretroviral therapy (ART)-naïve HIV-infected subjects and ART-treated individuals are now known to be characterized by having gut microbiomic dysbiosis, which is associated with a damaged intestinal barrier, impaired mucosal immunological functioning, increased microbial translocation, and long-term immune activation. Altered microbiota-related products in PLWH, such as lipopolysaccharide (LPS) and short-chain fatty acids (SCFA), have been associated with the development of leaky gut syndrome, favoring microbial translocation, which in turn has been associated with a chronically activated underlying host immune response and hence the facilitated pathogenesis of HBV infection. Herein, we critically review the interplay among gut microbiota, immunity, and HIV and HBV infection, thus laying down the groundwork with respect to the future development of effective strategies to efficiently restore normally diversified gut microbiota in PLWH with a dysregulated gut microbiome, and thus potentially reduce the prevalence of HBV infection in this population.
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Affiliation(s)
- Jing Ouyang
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
| | - Silvere D Zaongo
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
| | - Xue Zhang
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
| | - Miaomiao Qi
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
| | - Aizhen Hu
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
| | - Hao Wu
- Department of Infectious Diseases, You'an Hospital, Capital Medical University, Beijing, China
| | - Yaokai Chen
- Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China
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Khan AN, Bernardini J, Rault RM, Piraino B. Low Seroconversion with Hepatitis B Vaccination in Peritoneal Dialysis Patients. Perit Dial Int 2020. [DOI: 10.1177/089686089601600409] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Objective To compare seroconversion using hepatitis B vaccine between hemodialysis (HD) and peritoneal dialysis (PD) patients. Design Data on PD patients vaccinated were collected retrospectively for the period 1992 to 1995. The data on HD patients were collected prospectively from 1991 to 1994. Setting A university outpatient dialysis center. Participants All adult patients who received all four doses of hepatitis B vaccine while on dialysis were included (47 PD and 50 HD patients). Intervention Recombinant hepatitis B vaccine (Engerix), 40 μg IM was administered at 0, 1, 2, and 6 months. Main Outcome Measure Seroconversion was measured after completion of the vaccination series. Results 74% of the HD patients seroconverted compared to 53 % of PD patients (p = 0.03). Older, heavier patients compared to all the other patients had a lower seroconversion rate in both the HD patients (55 % vs. 78 %) and PD patients (38 % vs. 59 %) (p = 0.03). Conclusion The seroconversion rate to recombinant hepatitis B vaccine is lower in patients on PD than on HD for unclear reasons. Further studies are required to determine the etiology of this difference.
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Affiliation(s)
- Abdul N. Khan
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A
| | - Judy Bernardini
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A
| | - Raymond M. Rault
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A
| | - Beth Piraino
- Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A
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Stevens CE, Toy P, Kamili S, Taylor PE, Tong MJ, Xia GL, Vyas GN. Eradicating hepatitis B virus: The critical role of preventing perinatal transmission. Biologicals 2017; 50:3-19. [DOI: 10.1016/j.biologicals.2017.08.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Revised: 08/12/2017] [Accepted: 08/14/2017] [Indexed: 12/19/2022] Open
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Morsica G, Bagaglio S, Spagnuolo V, Castagna A, Di Serio C, Galli A, Della Torre L, Andolina A, Pramov A, Uberti-Foppa C. Immune response to hepatitis B vaccination in HIV-positive individuals with isolated antibodies against hepatitis B core antigen: Results of a prospective Italian study. PLoS One 2017; 12:e0184128. [PMID: 28863182 PMCID: PMC5581175 DOI: 10.1371/journal.pone.0184128] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 08/18/2017] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND AND AIM Antibodies against hepatitis B core antigen (anti-HBc) are found in 14-44% of patients with HIV infection, but it is still unclear whether hepatitis B virus (HBV) vaccination should be recommended for HIV-positive subjects with isolated anti-HBc (IAHBc). We examined the rate of anamnestic and primary responses (ARs and PRs) and associated factors in a group of HIV-infected patients with an IAHBc profile. METHODS This prospective study recruited 25 HIV-positive patients with anti-HBc alone who were vaccinated against HBV infection. Those without an AR (anti-hepatitis B envelope antigen [anti-HBs] levels of <10 U/L) or who were hypo-responsiveness (anti-HBs levels of >10 but <100 U/L) four weeks after the first dose of vaccine underwent a full course of vaccinations. Their clinical and virological data, including the presence of occult hepatitis B infection (OBI), were evaluated in accordance with the vaccination schedule. RESULTS Six of the 25 patients (24%) showed an AR, four of whom had anti-HBs levels of <100 U/L. Ten of 19 (52.6%) remaining patients became seroprotected after the third dose. OBI was detected in four of the six patients with an AR, two of the 10 patients with a PR, and none of the nine patients who did not respond. Multivariate analysis showed that an AR was associated with the presence of OBI (P = 0.0162), and a PR was associated with HCV antibody status. (P = 0.0191). CONCLUSIONS Our data suggest that testing for anti-HBc alone may not be a reliable means of assessing protection from HBV infection in HIV-positive patients. OBI-positive patients may benefit from a single vaccine dose. Anti-HCV serostatus may affect PRs.
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Affiliation(s)
- Giulia Morsica
- Division of Infectious Diseases, IRCCS, Ospedale San Raffaele, Milan, Italy
- * E-mail:
| | - Sabrina Bagaglio
- Division of Infectious Diseases, IRCCS, Ospedale San Raffaele, Milan, Italy
| | | | | | - Clelia Di Serio
- Vita-Salute San Raffaele University, CUSSB (University Centre for Statistics in the Biomedical Sciences), Milan, Italy
| | - Andrea Galli
- Division of Infectious Diseases, IRCCS, Ospedale San Raffaele, Milan, Italy
| | | | - Andrea Andolina
- Division of Infectious Diseases, IRCCS, Ospedale San Raffaele, Milan, Italy
| | - Alexander Pramov
- Vita-Salute San Raffaele University, CUSSB (University Centre for Statistics in the Biomedical Sciences), Milan, Italy
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Viral Infections, an Overview with a Focus on Prevention of Transmission. INTERNATIONAL ENCYCLOPEDIA OF PUBLIC HEALTH 2017. [PMCID: PMC7150291 DOI: 10.1016/b978-0-12-803678-5.00514-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Vitse CL, Poland GA. Writing a scientific paper-A brief guide for new investigators. Vaccine 2016; 35:722-728. [PMID: 28024957 DOI: 10.1016/j.vaccine.2016.11.091] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Revised: 11/21/2016] [Accepted: 11/30/2016] [Indexed: 10/20/2022]
Abstract
When applying for funding, researchers must demonstrate their productivity. For most funding organizations, a key measure of productivity is the number of papers published. The road to publication is rarely straightforward; few journals provide practical guidance to researchers who are struggling to publish their data. Here, we outline the sections of a research paper and describe practical steps in each part of the publication process as an aid to newer authors.
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Coverage and Long-Term Immunogenicity of Hepatitis B Vaccine in Healthcare Workers. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2016. [DOI: 10.5812/archcid.35758] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Pollack TM, Trang LTT, Ngo L, Cuong DD, Thuy PT, Colby DJ. Response to hepatitis B vaccination among HIV-infected adults in Vietnam. J Virus Erad 2016. [DOI: 10.1016/s2055-6640(20)30471-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Chi-Chung Cheng V, Fuk-Woo Chan J, FN Hung I, Yuen KY. Viral Infections, an Overview with a Focus on Prevention of Transmission. REFERENCE MODULE IN BIOMEDICAL SCIENCES 2016. [PMCID: PMC7157453 DOI: 10.1016/b978-0-12-801238-3.90174-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Lee MH. The Positive Rates of Anti-HBs and Titers of Antibody after Hepatitis B Vaccination. KOREAN JOURNAL OF CLINICAL LABORATORY SCIENCE 2015. [DOI: 10.15324/kjcls.2015.47.2.78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Affiliation(s)
- Mi-Hwa Lee
- Department of Medical Laboratory Science, Jinju Health College, Jinju 660-757, Korea
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Caubet JC, Ponvert C. Vaccine allergy. Immunol Allergy Clin North Am 2015; 50:132-137. [PMID: 25017679 DOI: 10.1016/j.iac.2014.04.004] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2021] [Accepted: 02/04/2022] [Indexed: 12/01/2022]
Abstract
Overdiagnosis of vaccine allergy is considered a major public health problem. This article discusses the different types of allergic reactions after immunization based on the timing (immediate vs nonimmediate) and the extent of the reaction (local vs systemic). The vaccine components potentially responsible for an allergic reaction are discussed, as well as the management of patients with a history of reaction to a specific vaccine and those with a history of allergy to one of the vaccine components.
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Affiliation(s)
- Jean-Christoph Caubet
- Department of Pediatrics, University Hospitals of Geneva and Medical School, University of Geneva, Geneva, Switzerland.
| | - Claude Ponvert
- Pulmonology & Allergology Service, Department of Pediatrics, Sick Children's Hospital, Paris, France
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Li J, Hu J, Liang X, Wang F, Li Y, Yuan ZA. Predictors of Poor Response After Primary Immunization of Hepatitis B Vaccines for Infants and Antibody Seroprotection of Booster in a Metropolis of China. Asia Pac J Public Health 2013; 27:NP1457-66. [DOI: 10.1177/1010539513496136] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
To evaluate proportion and predictors of poor response in infants and appraise booster seroprotection, we surveyed 2047 infants in Shanghai and detected antibody to hepatitis B (HB) surface antigen (anti-HBs). Poor responders were randomized into 2 groups, given booster with 5 µg and 10 µg hepatitis B vaccine (HepB), respectively. Proportion of infants with titer <10 mIU/mL and 10 to 99 mIU/mL was 1.86% and 15.14%, respectively. Multivariate logistic regression suggested infants of male, aged 13 to 18 months, premature, administered with 5 µg HepB or mother positive for HB surface antigen (HBsAg) and HBe antigen (HBeAg) would more likely develop worse response. Difference of geometric mean concentration between the first and full booster was not statistically significant both for 5 µg and for 10 µg HepB groups. The seroprotective rate were higher for infants with 10 µg HepB than those with 5 µg HepB ( P > .05). Therefore, it is concluded that booster for poor vaccinees with 10 µg HepB could achieve satisfactory seroprotection.
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Affiliation(s)
- Jian Li
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Jiayu Hu
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Xiaofeng Liang
- Chinese Center for Disease Control and Prevention, Beijing, China
| | - Fuzhen Wang
- Chinese Center for Disease Control and Prevention, Beijing, China
| | - Yanting Li
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
| | - Zheng-an Yuan
- Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China
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Gestational zinc deficiency impairs humoral and cellular immune responses to hepatitis B vaccination in offspring mice. PLoS One 2013; 8:e73461. [PMID: 24069198 PMCID: PMC3775768 DOI: 10.1371/journal.pone.0073461] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2013] [Accepted: 07/19/2013] [Indexed: 01/31/2023] Open
Abstract
Background Gestational zinc deficiency has been confirmed to impair the infant immune function. However, knowledge about effects of maternal mild zinc deficiency during pregnancy on hepatitis B vaccine responsiveness in offspring is limited. In this report, we aimed to examine how maternal zinc deficiency during pregnancy influences humoral and cellular immune responses to hepatitis B vaccination in offspring of BALB/c mice. Methodology/Principal Findings From day 1 of pregnancy upon delivery, maternal mice were given a standard diet (30 mg/kg/day zinc), zinc deficient diet (8 mg/kg/day zinc), or combination of zinc deficient diet (8 mg/kg/day zinc in the first 2 weeks of gestation) and zinc supplement diet (150 mg/kg/day zinc for the last week of pregnancy), respectively. Newborn pups of these maternal mice were immunized with hepatitis B vaccine at postnatal weeks 0, 2 and 4. Then, splenocytes and blood samples from the offspring mice were harvested for detection of serum zinc concentrations, humoral and cell-mediated immune responses, expression of cytokines using ELISA, CCK-8 and flow cytometric analysis. Results from the present study demonstrated that gestational zinc deficiency inhibited antibody responses, and decreased the proliferative capacity of T cells in offsprings immunized with hepatitis B vaccine. Additionally, HBsAg-specific cytokines analysis revealed that gestational zinc deficiency could inhibit secretion of IFN-γ from splenocytes, and decrease IFN-γ expression of CD4+ and CD8+ T cells. Conclusions/Significance Gestational zinc deficiency can weaken the humoral and cell-mediated immune responses to hepatitis B vaccine via decreasing B cell counts and hepatitis B virus-specific immunoglobulin G production, as well as reducing T cell proliferation, CD4+/CD8+ T cell ratio, and Th1-type immune responses.
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Al-Naamani K, Al-Maqbali A, Al-Sinani S. Characteristics of hepatitis B infection in a sample of omani patients. Sultan Qaboos Univ Med J 2013; 13:380-5. [PMID: 23984022 DOI: 10.12816/0003259] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2012] [Revised: 01/17/2013] [Accepted: 04/14/2013] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES This study aimed to describe the demographic and virological characteristics of chronic hepatitis B virus (HBV) infection in a sample of Omani patients, and indirectly assess the efficacy of hepatitis B vaccination programmes and catch-up strategies. METHODS A retrospective study was undertaken of all patients with chronic HBV infections evaluated and followed-up at the Hepatology Clinic of the Armed Forces Hospital (AFH), Muscat, Oman, between January 2009 and April 2011. RESULTS A total of 154 patients met the inclusion criteria. The mean age of infected patients was 33 years with 72.7% being over 27 years. Females constituted 47.7% of the patients. Half of the cohort was referred either from the AFH's Obstetric Clinic (29.2%) or its Blood Bank (22.1%). A family history of chronic HBV infection was present in 70% of patients. A total of 95% had positive hepatitis B surface antigens, while only 5% had isolated total hepatitis B core antibodies. Most patients (96%) were hepatitis B e-antigen-negative. The majority (77.9%) had low HBV dioribonucleic acid levels of <2,000 IU/ml. Radiological features of liver cirrhosis were observed in 5%. Patients requiring treatment were in the minority (9%). CONCLUSION Almost 50% of the infected patients were female, the majority being of childbearing age. Medical authorities in Oman should consider enforcing a screening policy for all pregnant women using complete hepatitis B serological testing.
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Fakharzadeh S, Kalanaky S, Hafizi M, Goya MM, Masoumi Z, Namaki S, Shakeri N, Abbasi M, Mahdavi M, Nazaran MH. The new nano-complex, Hep-c, improves the immunogenicity of the hepatitis B vaccine. Vaccine 2013; 31:2591-7. [PMID: 23583463 DOI: 10.1016/j.vaccine.2013.03.030] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Revised: 03/07/2013] [Accepted: 03/19/2013] [Indexed: 10/27/2022]
Abstract
Prevention of hepatitis B requires a vaccine that stimulates the humoral and cellular immune responses in a balanced manner, particularly those associated with Th1 and cytotoxic T cells. Alum adjuvant is currently used in the hepatitis B vaccine formulations but it lacks the efficiency of establishing such immune responses. Therefore, for accessing a suitable vaccine to prevent this fatal disease, it is essential to design and construct a new adjuvant which can overcome the limitations of the alum adjuvant and can stimulate a strong Th1 response as used along with it. In the present study, the adjuvant effect of Hep-c, the first nano-complex which was synthesized by nanochelating technology to improve the immunogenicity of the vaccine against hepatitis B, had been evaluated. Female Balb/c mice were divided into 7 groups and were injected with 10μg/ml of the hepatitis B vaccine and different doses of Hep-c for 3 times. Groups merely treated with the vaccine, Hep-c or phosphate buffered solution were used as control. Total specific antibody, IgG1, IgG2a, IgG2b, IgM, interleukin-4 (IL-4) and interferon-gamma (IFN-γ) levels were examined by the ELISA method. The proliferative response of the splenocytes was evaluated using bromodeoxyuridine assay. Results showed that immunization with hepatitis B vaccine and Hep-c increased the lymphocyte proliferation and specific IgM and IgG2a compared to the hepatitis B vaccine immunized group. Also, this nano-complex significantly increased the IFN-γ and IL-4 cytokine levels compared to the hepatitis B vaccine immunized group. Our findings show that Hep-c can not only preserve the alum capacity to effectively stimulate production of the antibodies but also cover its inefficiency in inducing Th1 response and prompting cellular immunity. Thus, by boosting the performance of the hepatitis B vaccine, it seemed that this nano-adjuvant has the suitable potential to be used in the commercial HBS vaccine formulation.
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Affiliation(s)
- Saideh Fakharzadeh
- Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran
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Ponvert C, Bloch-Morot É. Les réactions d’hypersensibilité allergiques et non allergiques aux vaccins. REVUE FRANCAISE D ALLERGOLOGIE 2013. [DOI: 10.1016/j.reval.2012.09.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Adult immunizations: updates and practical guidance for the practicing allergist-immunologist. Ann Allergy Asthma Immunol 2012; 109:295-302. [PMID: 23062382 DOI: 10.1016/j.anai.2012.03.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2012] [Revised: 03/16/2012] [Accepted: 03/20/2012] [Indexed: 11/20/2022]
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Seroprevalence of measles, mumps, rubella, varicella-zoster and hepatitis A-C in Emirati medical students. BMC Public Health 2012; 12:1047. [PMID: 23217121 PMCID: PMC3526402 DOI: 10.1186/1471-2458-12-1047] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2012] [Accepted: 11/27/2012] [Indexed: 01/28/2023] Open
Abstract
Background The aims of this study were to assess the seroprevalence of vaccine-preventable infections in Emirati medical students, and to provide scientific evidence for implementation of a cost-effective immunization guideline and policy for medical school admission. Methods This prospective cohort study involved 261 (61% female) Emirati medical students (preclinical and clinical) attending the College of Medicine and Health Sciences at UAE University. Data on vaccination and history of infectious diseases were collected from participants. Blood samples were collected between July 1, 2011 and May 30, 2012 for serological testing and QuantiFERON®-TB assay. Results All students tested negative for infection with hepatitis C virus and human immunodeficiency virus. The prevalence of seropositivity to rubella virus was 97%, varicella–zoster virus 88%, mumps virus 84%, measles virus 54%, hepatitis B virus (HBV) 48%, and hepatitis A virus 21%. The QuantiFERON®-TB test was positive in 8% and indeterminate in 2%. Forty percent of students received HBV vaccine at birth; their HBV titers (mean ± SD) were 17.2 ± 62.9 mIU/mL (median = 1.64). The remaining 60% received it at school and their titers were 293.4 ± 371.0 mIU/mL (median = 107.7, p = 0.000). Conclusion About 50% of students were susceptible to HBV and measles virus; therefore, pre-matriculation screening for antibodies against these viruses is highly recommended. Moreover, tuberculosis screening is necessary because of the high influx of expatriates from endemic areas. Students with inadequate protection should be reimmunized prior to contact with patients.
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Chou HY, Lin XZ, Pan WY, Wu PY, Chang CM, Lin TY, Shen HH, Tao MH. Hydrogel-Delivered GM-CSF Overcomes Nonresponsiveness to Hepatitis B Vaccine through the Recruitment and Activation of Dendritic Cells. THE JOURNAL OF IMMUNOLOGY 2010; 185:5468-75. [DOI: 10.4049/jimmunol.1001875] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Roukens AH, Vossen AC, Boland GJ, Verduyn W, van Dissel JT, Visser LG. Intradermal hepatitis B vaccination in non-responders after topical application of imiquimod (Aldara). Vaccine 2010; 28:4288-93. [PMID: 20433806 DOI: 10.1016/j.vaccine.2010.04.029] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2010] [Revised: 04/07/2010] [Accepted: 04/13/2010] [Indexed: 10/19/2022]
Abstract
BACKGROUND Five to ten percent of immunocompetent persons fail to develop a protective immune response to hepatitis B vaccination, and are defined non-responders (NR). We investigated the immune response to intradermal hepatitis B vaccination after pre-treatment of the skin with the TLR7 agonist imiquimod. METHODS Twenty-one non-responders (anti-HBs <10 IU/l after at least 6 intramuscular hepatitis B vaccinations) were randomly assigned to the control group (N=11) or the experimental group (N=10). Participants in both groups received 3 intradermal (ID) vaccinations with 5 microg HBsAg (0.125 mL) at 0, 1 and 6 months. In the experimental group, the dermal site of injection was pre-treated with 250 mg imiquimod ointment. Anti-HBs antibodies were determined at 0, 1, 2, 6 and 7 months. RESULTS In both study groups, 70% of the participants developed a protective immune response (anti-HBs >or=10 IU/l), after the 3rd intradermal vaccination. CONCLUSION The application of imiquimod on the skin prior to intradermal vaccination did not enhance the humoral response to hepatitis B vaccine. However, irrespective of imiquimod application, 70% of the NR who had not responded to 6 previous intramuscular vaccinations, developed a protective immune response with high affinity antibodies after 3 ID hepatitis B vaccinations with 5 microg HBsAg.
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Affiliation(s)
- Anna H Roukens
- Department of Infectious Diseases, Leiden University Medical Center, The Netherlands.
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24
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Kozłowska J, Mikuła T, Staćczak W, Wiercićska-Drapało A. Hepatitis B prophylaxis in HIV-infected patients. HIV & AIDS REVIEW 2010. [DOI: 10.1016/s1730-1270(11)60002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Abstract
BACKGROUND Hepatitis B virus (HBV) vaccination is recommended for all individuals with renal failure. Nevertheless, the response rate for this vaccine in hemodialysis (HD) patients is low, ranging from 50% to 80%. The goal of this study was to determine patient characteristics at the initiation of HD that influence HBV vaccine response. METHODS Patients new to HD in an urban population in the United States were retrospectively examined. Analyzed patients were HBV antibody and antigen negative and hepatitis C virus antibody negative at the start of HD, who received HBV recombinant vaccine. Nonresponse was defined as failure to seroconvert (>10 UI/L) after six deltoid intramuscular injections of vaccine. Response was defined as a lasting seroconversion (at least two consecutive positive titers) with </=6 injections. Demographic, laboratory, and kinetic modeling data were examined. RESULTS A total of 33 nonresponders and 64 responders were identified. Univariate analysis demonstrated that nonresponders were older (59 vs. 51 years), had a higher prevalence of diabetes mellitus (DM) (70 vs. 39%), had lower serum albumin levels (3.2 vs. 3.3 g/dL), and had higher dry weights (84 vs. 71 kg) than responders at HD start. In addition, nonresponders had lower normalized protein catabolic rates (0.74 vs. 0.85 g/kg/day) and lower (single-pool) spKt/V(urea)values (0.95 vs. 1.19). Nonresponders had lower serum creatinine levels than responders, despite the greater dry weights. In a multiple logistic analysis model, the presence of DM, age >/= 55 years, body weight >/=80 kg, and normalized protein catabolic rate </=0.75 g/kg/day were associated with HBV vaccination nonresponse. At the end of the vaccination period, nonresponders versus responders continued to have lower serum albumin (3.5 vs. 3.8 g/dL) and creatinine levels (7.8 vs. 10.0 mg/dL) and spKt/V(urea)(1.27 vs. 1.39). CONCLUSION Hepatitis B vaccine nonresponders on HD are older, are more likely to have DM, are more malnourished, and have lower spKt/V(urea) than responders. Nonresponders may also have a different body composition with a lower ratio of lean to total body mass.
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Affiliation(s)
- Andrew I Chin
- Division of Nephrology, University of California at Davis, Sacramento, California, U.S.A.
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Kim HN, Harrington RD, Crane HM, Dhanireddy S, Dellit TH, Spach DH. Hepatitis B vaccination in HIV-infected adults: current evidence, recommendations and practical considerations. Int J STD AIDS 2009; 20:595-600. [PMID: 19710329 DOI: 10.1258/ijsa.2009.009126] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Immunization with hepatitis B (HBV) vaccine is recommended for all HIV-infected individuals without immunity to HBV. This patient population, however, has relatively poor HBV vaccine responses. Factors associated with this impaired HBV vaccine response in HIV-infected individuals may include older age, uncontrolled HIV replication, and low nadir CD4 cell count. Postvaccination testing for HBV surface antibody is recommended and vaccine non-responders should undergo repeat immunization with a full series. The benefit of double dosage, the appropriate strategy for HIV-infected patients with isolated HBV core antibody and the timing and number of vaccinations in persons with advanced immunosuppression on highly active antiretroviral therapy remain controversial areas.
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Affiliation(s)
- H N Kim
- Division of Allergy & Infectious Diseases, Department of Medicine, University of Washington, Harborview Medical Center, Seattle, WA, USA.
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Kim HN, Harrington RD, Van Rompaey SE, Kitahata MM. Independent clinical predictors of impaired response to hepatitis B vaccination in HIV-infected persons. Int J STD AIDS 2008; 19:600-4. [PMID: 18725550 PMCID: PMC2690573 DOI: 10.1258/ijsa.2007.007197] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Protective response rates to hepatitis B (HB) vaccination have been reported as low as 18-62% in HIV-infected persons. The relative importance of various predictors for this poor response has not been fully characterized. In this retrospective cohort study, we examined the relationship between clinical characteristics and vaccine non-response (HB surface antibody <10 IU/L) among patients attending an urban HIV clinic. Among the 97 patients who met the inclusion criteria, 43 (44%) developed a protective antibody response. In multivariate analyses, age >40 years (odds ratio [OR] 3.03 [95% confidence interval [CI], 1.14-8.06]; P = 0.026) and alcohol abuse (OR 4.92 [95% CI, 1.72-20.89]; P = 0.007) were independent predictors of failure to develop vaccine response. In addition, CD4 nadir <200 (OR 7.24 [95% CI, 1.91-27.41]; P = 0.004), rather than CD4 current to vaccination, remained a strong independent risk factor. Patients with HIV viral suppression on highly active antiretroviral therapy had a significantly lower rate of vaccine failure (OR 0.31 [95% CI, 0.11-0.91]; P = 0.033), after adjusting for these other covariates. Our findings underscore the importance of confirming seroconversion after HB vaccination in HIV-infected patients and initiating vaccination early in the course of HIV infection.
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Affiliation(s)
- H Nina Kim
- Department of Medicine, Harborview Medical Center, University of Washington, Seattle, WA, USA.
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Nemes E, Lefler E, Szegedi L, Kapitány A, Kovács JB, Balogh M, Szabados K, Tumpek J, Sipka S, Korponay-Szabó IR. Gluten intake interferes with the humoral immune response to recombinant hepatitis B vaccine in patients with celiac disease. Pediatrics 2008; 121:e1570-6. [PMID: 18519462 DOI: 10.1542/peds.2007-2446] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE Patients with celiac disease, who often carry human leukocyte antigen-DR3;DQ2, are prone to inadequate response to hepatitis B immunization. We evaluated vaccine response in relation to disease activity and whether previous treatment with a gluten-free diet influences the achievement of protective antibody titers. PATIENTS AND METHODS We studied 128 children and adolescents with celiac disease and 113 age-matched control subjects. Twenty-two patients with celiac disease were prospectively immunized after diagnosis during dietary treatment (group 1). A total of 106 (group 2) and the control subjects received vaccination by mass immunization in schools at 14 years of age regardless of diet status and when celiac disease was still undiagnosed in 27 of these children. Diet compliance and celiac disease activity were monitored by measurement of antibodies against transglutaminase and endomysium. Vaccine response was determined by measuring antihepatitis B antibodies from serum. RESULTS The seroconversion after hepatitis B vaccination was 95.5% in group 1. All of these patients carried human leukocyte antigen DQ2. The response rate in group 2 was 50.9% and correlated with gluten intake (untreated patients: 25.9%, non-strict diet: 44.4%, strict diet: 61.4%). Treated and compliant patients did not significantly differ from control subjects (75.2%). Thirty-seven antihepatitis B-negative patients with celiac disease received a booster during a controlled gluten-free diet, and 36 (97.3%) seroconverted, irrespective of the presence of human leukocyte antigen DQ2. CONCLUSIONS Nonresponse to recombinant hepatitis B surface antigen may be a sign of undiagnosed celiac disease. However, there is a good vaccine response in adequately treated patients. Human leukocyte antigen DQ alleles do not seem to have a primary role. Revaccination is recommended during a controlled gluten-free diet.
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Affiliation(s)
- Eva Nemes
- Department of Pediatrics, Medical and Health Science Center, University of Debrecen, Nagyerdei krt 98, H-4032 Debrecen, Hungary.
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Weihrauch MR, Bergwelt-Baildon MV, Kandic M, Weskott M, Klamp W, Rösler J, Schultze JL. T cell responses to hepatitis B surface antigen are detectable in non-vaccinated individuals. World J Gastroenterol 2008; 14:2529-33. [PMID: 18442200 PMCID: PMC2708364 DOI: 10.3748/wjg.14.2529] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate, whether humoral hepatitis-B-vaccine non-responders also fail to mount a T cell response and to compare these results to normal vaccines.
METHODS: Fourty-seven health care employees were enrolled in this study including all available non-responders (n = 13) with an anti-HBsAg titer < 10 kU/L and all available low-responders (n = 12) with an anti-HBsAg titer < 100 kU/L. Also, 12 consecutive anti-HBsAg negative pre-vaccination subjects were enrolled as well as 10 subjects (+7 from the vaccinated group) with titers > 1000 kU/L as controls. PBMC from all subjects were analyzed by IFN-γ and IL-4 ELISPOT assays for the presence of hepatitis B surface antigen (HBsAg) reactive T cells.
RESULTS: Non-responders and low-responders had no or only very limited T cell responses, respectively. Individuals responding to vaccination with the induction of a high anti-HBsAg titer showed a strong T cell response after the third vaccination. Surprisingly, these individuals showed response even before the first vaccination. T cell response to control antigens and mitogens was similar in all groups.
CONCLUSION: Our data suggest that there is no general immune deficiency in non-/low-responders. Thus, we hypothesize that the induction of anti-HBsAg responses by vaccination is significantly dependent on the pre-existing T cell repertoire against the specific antigen rather than the presence of a general T cell defect.
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Alavian SM, Mansouri S, Abouzari M, Assari S, Bonab MS, Miri SM. Long-term efficacy of hepatitis B vaccination in healthcare workers of Oil Company Hospital, Tehran, Iran (1989-2005). Eur J Gastroenterol Hepatol 2008; 20:131-4. [PMID: 18188034 DOI: 10.1097/meg.0b013e3282f1cc28] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE This study was conducted to evaluate the 16-year efficacy of hepatitis B virus (HBV) vaccine in healthcare workers of Oil Company Hospital, Tehran, Iran. METHODS Two hundred healthcare workers were enrolled in the study in 1989. All HBV markers were tested and those with positive HBV markers, positive antihepatitis C virus or anti-HIV were excluded from the study. The remaining participants received three doses of HBV vaccine and again all of our participants were reevaluated in 2005. Hepatitis B surface antigen (HBsAg), antihepatitis B surface antibody (anti-HBsAb), and antihepatitis B core antibody (anti-HBcAb) were checked in all participants and those with anti-HBcAb above 10 IU/l were excluded from the final evaluation. RESULTS No participant was positive for HBsAg in either 1989 or 2005. Protective levels of anti-HBsAb were absent in all participants in 1989, but present in 67 (80.7%) participants in 2005 (P<0.001). Anti-HBsAb titer after vaccination was significantly higher in female participants than in male participants (P=0.01). Mean anti-HBsAb titer was 640+/-411.7 IU/l (range: 2-1000 IU/l) and the lowest protective titer was 12 IU/l. CONCLUSION According to our results, 80.7% of our participants had a protective titer of anti-HBsAb 16 years after vaccination. Although all anti-HBc positive participants were free of clinical hepatitis and were negative for HBsAg, hepatitis B vaccination was proved to be highly effective in preventing clinically significant infection and chronic carrier status up to 16 years after the primary vaccination. Hence, HBV revaccination may not be mandatory in healthcare workers, according to their sufficient long-term level of anti-HBsAb.
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Affiliation(s)
- Seyed-Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Brim N, Zaller N, Taylor LE, Feller E. Twinrix®vaccination schedules among injecting drug users. Expert Opin Biol Ther 2007; 7:379-89. [PMID: 17309329 DOI: 10.1517/14712598.7.3.379] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Twinrix is the only licensed vaccine that provides dual protection against infection with hepatitis A virus (HAV) and hepatitis B virus (HBV). The standard vaccination schedule for Twinrix is 0, 1 and 6 months. However, many high-risk populations, such as injecting drug users (IDUs), do not complete the vaccination series and, thus, do not acquire sufficient immunity against HAV and HBV. Twinrix can be administered using an accelerated vaccination schedule of 0, 7 and 21 days, with a booster recommended at 12 months. This manuscript reviews the available literature on vaccinating IDUs against HAV and HBV. The authors conclude that there is insufficient evidence regarding whether the accelerated Twinrix HAV/HBV vaccination schedule would yield a greater number of IDUs protected against both HAV and HBV.
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Affiliation(s)
- Nancy Brim
- Brown Medical School, Providence, Rhode Island, USA, 2The Miriam Hospital, 164 Summit Ave, Providence, RI 02906, USA.
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Daryani NE, Nassiri-Toosi M, Rashidi A, Khodarahmi I. Immunogenicity of recombinant hepatitis B virus vaccine in patients with and without chronic hepatitis C virus infection: A case-control study. World J Gastroenterol 2007; 13:294-8. [PMID: 17226912 PMCID: PMC4065961 DOI: 10.3748/wjg.v13.i2.294] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare the response of standard hepatitis B virus (HBV) vaccination between patients with chronic hepatitis C virus (HCV) infection and healthy individuals.
METHODS: This is a prospective case-control study. A total of 38 patients with chronic HCV infection and 40 healthy controls were included. Vaccination was performed by injection of 20 μg recombinant HBsAg into the deltoid muscle at mo 0, 1 and 6. Anti-HBs concentration was determined 3 mo after the last dose and compared between the two groups. The response pattern was characterized as (1) high-response when the anti-HBs antibody titer was > 100 IU/L, (2) low-response when the titer was 10-100 IU/L and (3) no-response when the titer was < 10 IU/L.
RESULTS: In the patient group, there were 10/38 (26.3%) non-responders, 8/38 (21.1%) low-responders and 20/38 (52.6%) high-responders. The corresponding values in the control group were 2/40 (5.0%), 7/40 (17.5%) and 31/40 (77.5%), respectively. The response pattern was statistically different between the two groups. In multivariate analysis, smoking was a significant confounder, while HCV infection lost its significant correlation with lower antibody response.
CONCLUSION: Patients with chronic HCV infection tend to respond weakly to HBV vaccination compared to healthy individuals, though this correlation is not independent according to multivariate analysis.
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Affiliation(s)
- Naser Ebrahimi Daryani
- Department of Gastroenterology, Medical School, Tehran University of Medical Sciences, Seyed Khandan, Tehran, Iran
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Estévez ZC, Betancourt AA, Muzio González V, Baile NF, Silva CV, Bernal FH, Arias EP, Delhanty Fernández A, Olazábal NM, del Río Martín A, Batista LL, Véliz Ríos G, Hernández HH, Hernández AB, Lugo EP, de la Torre Cruz J, Batista Marchec BL, Falcón LA, Brito JT, León DO, Saura PL. Immunogenicity and safety assessment of the Cuban recombinant hepatitis B vaccine in healthy adults. Biologicals 2006; 35:115-22. [PMID: 17056272 DOI: 10.1016/j.biologicals.2006.06.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2006] [Revised: 05/30/2006] [Accepted: 06/12/2006] [Indexed: 10/24/2022] Open
Abstract
Manufactures of biotechnological/biological products (including vaccines) frequently make changes to manufacturing processes of products both during development and after approval. In our case, a non-inferiority bridging study was carried out to demonstrate that changes in the production plant facilities of Cuban recombinant hepatitis B vaccine, Heberbiovac HB, did not affect the safety and immunogenicity of the vaccine. This controlled, randomized, doubled-blinded trial included 501 volunteers, aged between 20 and 64, who were given three doses of vaccine (20 microg HBsAg/mL) at month 0, 1, and 2. Four lots were evaluated (three corresponding to the new production facilities and a control one produced in the older facilities). One month after the third dose, were observed protective levels of anti-HBsAg in 97% of the subjects that concluded the study with a geometric mean antibody titer (GMT) of 931.18 IU/L. Normal values of body mass index (BMI), the younger ages, and being a female, were significantly related to a good antibody response. The vaccine was well tolerated. Pain at the injection site was the most commonly reported symptom. We conclude that Heberbiovac HB vaccine maintains its characteristics after the modifications carried out in the production plant facilities and both, lot obtained in previous facilities and in the new ones, are comparable in terms of safety and immunogenicity.
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Affiliation(s)
- Zurina Cinza Estévez
- Centre for Genetic Engineering and Biotechnology, Ave 31 e/158 y 190, P.O. Box 6162, 10600 Havana, Cuba.
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Aziz A, Aziz S, Li DS, Murphy L, Leone N, Kennedy M, Dhillon S, Van Thiel DH. Efficacy of repeated high-dose hepatitis B vaccine (80 microg) in patients with chronic liver disease. J Viral Hepat 2006; 13:217-21. [PMID: 16611186 DOI: 10.1111/j.1365-2893.2005.00674.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Patients with chronic liver disease (CLD) respond poorly to standard hepatitis B (HBV) vaccine given as sequential 20 microg IM shots because of an overall impaired immune response. Many of these patients go on to liver transplantation and are at risk of acquiring recurrent or de novo HBV infection. To evaluate the efficacy and safety of high-dose (80 microg) IM HBV vaccination in patients with CLD who had previously failed to respond to a standard three-dose schedule of 40 microg IM vaccine given monthly. A retrospective review was undertaken at our institution of 79 patients with CLD who were treated with high-dose (80 microg) HBV vaccinations. All had previously failed a three-dose course of 40 microg HBV vaccine. An HBV vaccine response was defined as an anti-HBs titer greater than 100 mIU/ml. Liver enzymes, creatinine, age, prothrombin time, total vaccine dose, and MELD score were recorded. No adverse events were reported. Seventy-two per cent (57/79) of the subjects had an adequate response after receiving a mean total dose of 220 mug vaccine (range 80-800 microg). Twenty-eight per cent (22/79) of the subjects did not respond after receiving a mean total dose of 420 microg vaccine (range 240-720 microg). Non-responders had more severe hepatic disease defined as a higher mean total bilirubin level (p = 0.003) and a lower mean albumin level (p < 0.05). Age, prothrombin time, MELD score, and creatinine were not statistically significant between the responders and non-responders. Repeated high-dose (80 microg) HBV vaccination, in patients who do not respond to standard HBV vaccine doses, is safe and effective in the majority of patients with CLD.
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Affiliation(s)
- A Aziz
- Division of Gastroenterology, Nutrition and Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA.
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Abstract
BACKGROUND Hepatitis B virus (HBV) causes acute and chronic liver diseases. Hepatitis B vaccination is recommended for health-care workers. OBJECTIVES To assess the beneficial and harmful effects of hepatitis B vaccination in health-care workers. SEARCH STRATEGY We searched the trial registers of The Cochrane Hepato-Biliary Group, The Cochrane Library, MEDLINE, and EMBASE to February 2003. SELECTION CRITERIA Randomised trials comparing any dose, injection route, injection site, or schedule of hepatitis B plasma-derived vaccines (PDV) or recombinant vaccines (RV) versus placebo, no intervention, or another hepatitis B vaccine in health-care workers. DATA COLLECTION AND ANALYSIS Two reviewers extracted the data independently. The reviewers assessed the methodological quality of the trials regarding generation of the allocation sequence, allocation concealment, double blinding, and follow-up. The results were presented as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS We identified 21 randomised trials, all with one or more methodological weaknesses. Four trials demonstrated that PDV versus placebo significantly decreased hepatitis B events at maximum follow-up (RR 0.51, 95% CI 0.35 to 0.73). RV did not differ significantly from PDV in eliciting a protective hepatitis B surface antibody (anti-HBs) level in two trials. Both vaccines were well tolerated. Low-dose vaccine (1 or 2 microg) by the intradermal route resulted in significantly more participants without protective anti-HBs level compared with high-dose (10 or 20 microg) by the intramuscular route (RR 1.41, 95% CI 1.13 to 1.76). The intradermal route caused significantly more local adverse events, while the intramuscular route caused significantly more systemic adverse events. The gluteal injection produced significantly more participants without protective anti-HBs level than the deltoid injection. The prevalence of anti-HBs seroconversion by rapid vaccination (0, 1, and 2 months) was significantly lower than that by standard vaccination (0, 1, and 6 months). Booster vaccinations with different RV doses (2.5, 5, 10, 20, or 40 microg) produced similar prevalence of anti-HBs seroconversion in three trials assessing participants who did not respond to previous HBV vaccination. AUTHORS' CONCLUSIONS PDV significantly prevents hepatitis B events. RV seems to be able to elicit similar protective anti-HBs levels. The intramuscular route with 20 microg RV was significantly more effective compared with the intradermal route with 2 microg RV as was the standard schedule compared with a rapid schedule and deltoid intramuscular injection compared with the gluteal intramuscular injection. It is unclear if booster vaccination of non-responders offers higher anti-HBs seroconversion and hepatitis B vaccine prevents the infection of hepatitis B mutants in health-care workers.
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Affiliation(s)
- W Chen
- Toronto Western Hospital, University Health Network, University of Toronto, Liver Clinic, Room 181, 6B Fell Pav, 399 Bathurst St., Toronto, Ontario, Canada M5T 2S8.
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Albarran B, Goncalves L, Salmen S, Borges L, Fields H, Soyano A, Montes H, Berrueta L. Profiles of NK, NKT cell activation and cytokine production following vaccination against hepatitis B. APMIS 2005; 113:526-35. [PMID: 16086823 DOI: 10.1111/j.1600-0463.2005.apm_191.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Human natural killer (NK) cells (CD56+ CD3-) represent crucial components of the innate immune system especially against viral infections and because their activation can modulate the outcome of the adaptive immune response. NKT cells (CD56+CD3+), a lymphocyte T population characterized by expression of surface markers of NK cells, are known to be abundant in the liver and their activation could be associated with hepatic injury. Using three-color flow cytometry to measure surface receptors and intracellular cytokines, we have explored early activation signals and cytokine production in NK and NKT cells within a group of hepatitis B vaccinated and non-vaccinated individuals. A specific increase of the CD56bright cell population, the activation receptor CD69 and IFN-gamma, was observed in NK cells following incubation with recombinant HBsAg in responders to vaccination. Comparable results were observed in NKT cells showing an increment of CD69, CD25, IL-2 and IFN-gamma expression in responder subjects. These parameters were statistically diminished in non-responder individuals (p<0.05) in both groups of cells. These results demonstrate a diminished activation of these cells in non-responders to the vaccine, suggesting that NK and NKT cells play an important role in the immune response following hepatitis B vaccination.
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Affiliation(s)
- B Albarran
- Institute of Clinical Immunology, University of Los Andes, Merida, Venezuela
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Godkin A, Davenport M, Hill AVS. Molecular analysis of HLA class II associations with hepatitis B virus clearance and vaccine nonresponsiveness. Hepatology 2005; 41:1383-90. [PMID: 15915462 DOI: 10.1002/hep.20716] [Citation(s) in RCA: 104] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Clearance of acute hepatitis B virus (HBV) infection is associated with a vigorous CD4+ T-cell response focusing on the core protein. HLA class II glycoproteins present viral peptides to CD4+ T cells and influence the immune responses. HLA-DRB1*1301/2 have been associated with viral clearance, and HLA-DRB1*0301 is associated with nonresponse to vaccination with envelope proteins. Binding affinities of overlapping peptides covering the core and envelope proteins of HBV were measured to HLA glycoproteins encoded by HLA-DRA1*0101,-DRB1*0101 (HLA-DR1), HLA-DRA1*0101,-DRB1*0301 (HLA-DR3), HLA-DRA1*0101,-DRB1*0701 (HLA-DR7) and HLA-DRA1*0101,-DRB1*1301 (HLA-DR13) molecules and compared with published peptide-specific CD4+ T-cell responses. There are more high-affinity ligands (IC50 < 1 micromol/L) derived from the core protein than the surface antigen (P < .04 for HLA-DR1/7/13), but there was no increase in the number or the affinity of ligands for HLA-DR13. Clusters of particular core peptides bound to multiple HLA types, explaining the immunodominance of these regions for T-cell responses. Within the envelope protein, the low-affinity ligands (IC50 < 10 micromol/L) are found mainly in the surface antigen, with a marked paucity of ligands for HLA-DR3 (HLA-DR3 vs. non-DR3; P < .05) consistent with the lower vaccination responses for this HLA type. Of all peptides tested, 8 to 10 bound mainly to one HLA type, allowing a substantially greater breadth of response in heterozygotes. In conclusion, these data offer a mechanistic explanation for the dominant response to the HBV core protein during infection and support the direct involvement of the HLA-DRB1 gene in vaccine nonresponsiveness but not altered susceptibility to viral persistence.
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Affiliation(s)
- Andrew Godkin
- Cellular Immunology and Vaccine Development Group, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
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Jarrosson L, Kolopp-Sarda MN, Aguilar P, Béné MC, Lepori ML, Vignaud MC, Faure GC, Kohler C. Most humoral non-responders to hepatitis B vaccines develop HBV-specific cellular immune responses. Vaccine 2004; 22:3789-96. [PMID: 15315860 DOI: 10.1016/j.vaccine.2004.02.046] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2004] [Accepted: 02/29/2004] [Indexed: 11/25/2022]
Abstract
About 10% of health care professionals vaccinated against hepatitis B virus (HBV) fail to develop protective antibodies. We tested the capacity of peripheral blood lymphocytes from 121 health care professionals, including 76 non-responders, to proliferate to four HBV vaccines, examined the proliferating cells' subset, production of IFN-gamma, IL-4 and IL-10, and for 22 subjects, the cytokine production genotype. Specific proliferative responses to at least one HBV antigen were noted in 75% humoral non-responders. These cells differed from the CD4+ strongly proliferating cells of responders. Non-responders frequently displayed a genotype of high TGF-beta and intermediate IL-10 secretion. Most humoral non-responders to HBV thus develop specific cellular immune responses, eventually liable to protect them against viral infection.
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Affiliation(s)
- L Jarrosson
- Laboratoire d'Immunologie du CHU, Faculté de Médecine, BP 184, 54500 Vandoeuvre-les-Nancy, France
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Sorabjee JS, Garje R. Vaccinated but not immunized: protection against hepatitis B in medical staff in the developing world. J Hosp Infect 2004; 58:164-5. [PMID: 15474194 DOI: 10.1016/j.jhin.2004.06.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2004] [Indexed: 10/26/2022]
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de Sousa Júnior JX, de Monte Neto JT, de Castro JAF, de Andrade HM, do Monte SJH. [Association of humans leucocitary antigens with humoral nonresponsive to hepatitis B vaccine in chronic hemodialysis patients]. Rev Soc Bras Med Trop 2004; 37:15-7. [PMID: 15042175 DOI: 10.1590/s0037-86822004000100004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Vaccination using surface antigen from hepatitis B virus has not been successfully responded by hemodialysis patients. The present study was aimed at assessing a possible relationship between human leukocyte antigens and the low production of protective antibodies (anti-HbS) against the surface antigen from hepatitis B by patients with chronic renal failure submitted to hemodialysis programs. The antigens HLA-DR and HLA-DQ were identified in 76 hemodialysis patients through classic microlymphotoxicity. Our results showed that 34.2% of the patients were non-responsive to the vaccine VHB. The most frequent HLA specificity were: HLA-DR3, DR-7 and DQ2 with a significant association for HLA-DR3 (p=0.0025; OR 5.1; IC 95% 1.36-19.10). Such data suggest an association between genes from HLA class II antigens and the humoral non-response to the vaccine VHB.
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41
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Moore MA, Macpherson LMD, Kennedy C, Bagg J. Provision of hepatitis B vaccination for primary care dental staff in Scotland. J Infect 2003; 47:322-7. [PMID: 14556757 DOI: 10.1016/s0163-4453(03)00094-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVES All dental surgeons should be protected from hepatitis B virus (HBV) infection by immunisation, ideally administered and monitored via occupational health services (OHS). This study examined relevant OHS systems in place for dental primary care healthcare workers (DHCW) across all Health Board Areas (HBAs) in Scotland. It also explored the DHCWs' knowledge of, and access to, these systems in three HBAs. METHODS Data from senior staff in all Scottish Health Boards and Primary Care Trusts were collected by self-completing questionnaires. Information from DHCWs was collected via telephone interviews with General Dental Practitioners (GDPs) and Community Dental Officers (CDOs) in each of Ayrshire and Arran, Highland and Lothian Health Boards. RESULTS Thirteen of the 15 HBAs had robust HBV vaccination and monitoring systems. However, only 7/15 (47%) of these covered all DHCWs. Seven HBAs provided vaccination and monitoring for CDOs only, leaving GDPs to undertake these responsibilities for themselves. Of the 105 DHCWs approached, 82 gave an interview. These interviews highlighted major differences between HBAs in relation to access of DHCWs to OHS and indicated that CDOs had greater access than GDPs to OHS. Overall, 31% of DHCWs were not satisfied with the OHS available. CONCLUSION In order to safeguard both staff and patients, significant further work is required to ensure that all DHCWs have access to appropriate OHS support for provision and monitoring of immunisation procedures and related functions such as management of sharps injuries.
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Affiliation(s)
- M A Moore
- Community Dental Service, NHS Lanarkshire, Coathill Hospital, Coatbridge, UK
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Abstract
The major envelope protein of the hepatitis B virus (HBV), the HBsAg, constitutes the current preventative vaccine, which represents the first subunit viral vaccine developed. The genetics of the immune response to HBsAg has been extensively studied both in humans and mice. Murine studies begun over 20 years ago indicated that at least two MHC class II and one MHC class III genes regulate anti-HBs immune responses. Additional MHC-linked genes influence the immune responses to the higher molecular weight (pre-S) components of the HBV envelope. The murine studies predicted even more complex MHC gene regulation of human immune responses to the HBsAg and that complexity certainly has been demonstrated during the ensuing years. This brief review is an attempt to summarize our current understanding of the MHC genes that influence the immune response to the HBsAg and possible mechanisms of action.
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Affiliation(s)
- David R Milich
- The Vaccine Research Institute of San Diego, Department of Immunology, San Diego, CA 92109, USA.
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Antigen-specific T cell response in infants after recombinant hepatitis B virus vaccination at birth: evaluation of T helper lymphocyte diversity. Clin Immunol 2003; 107:122-8. [PMID: 12763481 DOI: 10.1016/s1521-6616(03)00047-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Recombinant hepatitis B virus antigen (rHBsAg)-specific CD4+ T cell clones (TCC) were isolated and expanded from the peripheral blood of nine children vaccinated at birth against the hepatitis B (HB) virus. Four of them responded with protective antibody production (responders), three subjects were unable to produce detectable antibody levels even after revaccination (nonresponders), and two infants produced antibodies only after revaccination (slow responders). TCC were then characterized for their ability to produce cytokines known to be important for T cell expansion (interleukin-2, IL-2) and/or effector functions (IL-4, IFN-gamma, IL-10). Results demonstrated that the frequency of rHBsAg-specific TCC in the samples of nonresponders was comparable to or higher than that in the samples of responders. Nevertheless, the majority of TCC obtained from responders or from slow responders before revaccination displayed the T helper 1 (T(H1))-dominant phenotype, while the majority of TCC obtained from nonresponders were nonpolarized T lymphocytes. After revaccination, the distribution of the different T(H) subsets in slow responders was heterogeneous. Overall, our present data suggest that an absence or delay in developing an rHBsAg-specific antibody response to vaccination is not associated with the capacity to generate an Ag-specific T cell response. However, compared to responders, nonresponding infants react to the rHBsAg vaccination with a reduced capacity to expand and differentiate toward polarized T(H) cells.
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De Maria N, Idilman R, Colantoni A, Van Thiel DH. Increased effective immunogenicity to high-dose and short-interval hepatitis B virus vaccination in individuals with chronic hepatitis without cirrhosis. J Viral Hepat 2001; 8:372-6. [PMID: 11555195 DOI: 10.1046/j.1365-2893.2001.00301.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Hepatitis B virus (HBV) vaccination is recommended for individuals with chronic liver disease. However, the response to standard doses of hepatitis B vaccines in such individuals has been poor. The aim of the present study was to assess the response to high-dose short-interval HBV vaccination in individuals with chronic liver disease of different aetiologies. A total two hundred and 24 subjects with chronic liver disease (138 chronic active hepatitis and 86 cirrhosis) and 26 healthy controls were vaccinated using a high-dose (40 microg) short-interval (monthly for 3 consecutive months) HBV vaccination schedule. One hundred and thirty-eight of the 224 subjects with chronic liver disease (62%) seroconverted to anti-HBs antibody positivity (>10 mIU/mL) after the third dose of vaccine as compared with 24 of the 26 controls (92%) (P < 0.01). The response rate was reduced in individuals with cirrhosis (36/86, 42%), particularly in alcohol-induced cirrhosis (2/17, 12%), as compared with individuals with chronic hepatitis (102/138, 74%) (P < 0.001). No significant HBV vaccination-related adverse effects were seen in individuals with or without cirrhosis as well as in the controls. High-dose short-interval HBV vaccination is safe and efficacious in individuals with chronic liver disease. The response to HBV vaccination is reduced in cirrhotics, particularly those with alcoholic cirrhosis. These data suggest that HBV vaccination should be accomplished early in an individual cause of chronic liver disease prior to the development of cirrhosis.
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Affiliation(s)
- N De Maria
- Loyola University Medical Center, Department of Medicine, Division of Gastroenterology and Liver Transplantation, Maywood, Illinois 60153, USA.
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45
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Alves AS, Nascimento CM, Granato CH, Sato HK, Morgato MF, Pannuti CS. Hepatitis B vaccine in infants: a randomized controlled trial comparing gluteal versus anterolateral thigh muscle administration. Rev Inst Med Trop Sao Paulo 2001; 43:139-43. [PMID: 11452321 DOI: 10.1590/s0036-46652001000300004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
A significantly diminished antibody response to hepatitis B vaccine has been demonstrated in adults when the buttock is used as the injection site. However, in Brazil, the buttock continues to be recommended as site of injection for intramuscular administration of vaccines in infants. In this age group, there are no controlled studies evaluating the immunogenicity of the hepatitis B vaccine when administered at this site. In the present study, 258 infants were randomized to receive the hepatitis B vaccine either in the buttock (n = 123) or in the anterolateral thigh muscle (n = 135). The immunization schedule consisted of three doses of hepatitis B vaccine (Engerix Bregister mark or target, 10 microg) at 2, 4 and 9 months of age. There were no significant differences in the proportion of seroconversion (99.3% x 99.2%), or in the geometric mean titer of ELISA anti-HBs (1,862.1 x 1,229.0 mIU/mL) between the two groups. This study demonstrates that a satisfactory serological response can be obtained when the hepatitis B vaccine is administered intramuscularly into the buttock.
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Affiliation(s)
- A S Alves
- Laboratory of Virology, Instituto de Medicina Tropical de São Paulo, Department of Infectious Diseases, Faculdade de Medicina, Universidade de São Paulo, SP, Brasil
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Avanzini MA, Belloni C, Soncini R, Ciardelli L, de Silvestri A, Pistorio A, Tinelli C, Maccario R, Rondini G. Increment of recombinant hepatitis B surface antigen-specific T-cell precursors after revaccination of slow responder children. Vaccine 2001; 19:2819-24. [PMID: 11282192 DOI: 10.1016/s0264-410x(01)00007-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
The aim of the study was to investigate the in vitro T-cell response to recombinant hepatitis B (rHBsAg) in a group of children (defined as "slow responders") vaccinated at birth, presenting antibody levels < 10 mIU/ml after the vaccination schedule, and developing anti-rHBs antibodies after revaccination. T-cell mediated immune response towards rHBsAg was evaluated in 35 healthy children in "bulk" culture experiments (19 responders and 16 slow responders) and by limiting dilution analysis (nine responders and five slow responders) to quantify the frequency of proliferating T lymphocyte-precursors (PTL-p). Before the booster dose, lymphocytes from slow responder children failed to proliferate to rHBsAg, while a normal proliferation was observed in all responders. A statistically significant difference in rHBsAg-specific PTLp frequencies was observed between the two groups. Among the slow responder group, a significant increase of PTLp was observed after the supplementary vaccine dose.Nevertheless, PTLp frequencies remained significantly lower than those measured in responders. These results suggest a role for follow-up of slow responder children over time, in order to perform booster vaccination when inadequate anti-HBs titre is present.
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Affiliation(s)
- M A Avanzini
- Laboratori Sperimentali di ricerca -- Area trapiantologica -- Trapianto midollo osseo ed oncoematologia pediatrica, IRCCS Policlinico S. Matteo, 27100 Pavia, Italy.
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Larsen CE, Xu J, Lee S, Dubey DP, Uko G, Yunis EJ, Alper CA. Complex cytokine responses to hepatitis B surface antigen and tetanus toxoid in responders, nonresponders and subjects naive to hepatitis B surface antigen. Vaccine 2000; 18:3021-30. [PMID: 10825606 DOI: 10.1016/s0264-410x(00)00084-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Some human subjects vaccinated with hepatitis B surface antigen (HBsAg) do not produce antibodies to the vaccine (nonresponders). The mechanism for nonresponse is unknown. To understand the response and nonresponse to nominal antigens better, we determined the level and kinetics of cytokine secretion in response to HBsAg and tetanus toxoid (TT) by peripheral blood mononuclear cells (PBMC) in vitro from HBsAg vaccine responders and nonresponders and from individuals naive to HBsAg. Proliferating PBMC secreted peak levels of interleukin-2 (IL-2) at 2 days and peak levels of tumor necrosis factor-beta (TNF-beta), interferon-gamma (IFN-gamma), IL-4 and IL-10 at 3-6 days post-stimulation. In contrast, nonproliferating PBMC (whether from nonresponders, naive subjects or weak responders) did not produce detectable levels of TNF-beta or IFN-gamma, nor was IL-4 or IL-10 produced significantly, and that produced had a different kinetic profile from that of proliferating PBMC. HBsAg-specific cytokine production by PBMC from strong responders broadly paralleled their cytokine responses to TT. Cellular cytokine mRNA levels measured by reverse transcriptase-polymerase chain reaction corroborated the secreted cytokine results. The anti-HBsAg- and anti-TT-specific T cell cytokine responses were mixed Th(1/2)-like and donor-specific. An HBsAg-specific cytokine response, but not a TT-specific cytokine response, was completely missing in nonresponders. These data suggest that the T cell defect of HBsAg nonresponse is not due to a skewed cytokine profile.
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Affiliation(s)
- C E Larsen
- The Center for Blood Research, 800 Huntington Avenue, Boston, MA 02115, USA
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Abstract
Exposure to blood and body fluids that may be contaminated with infectious agents is a common occupational hazard for health care workers. Health care workers in the emergency department or out-of-hospital setting are at especially high risk for exposure to blood or body fluids. Nonemergency health care workers are frequently referred to hospital EDs for immediate treatment of occupation exposures. A series of recommendations by the Centers for Disease Control and Prevention evolved over the past decade, and changes are expected to continue. This state-of the-art article reviews current recommendations for management of persons exposed to blood or body fluids and discusses the scientific basis for recommendations regarding hepatitis B virus, hepatitis C virus, and HIV.
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Affiliation(s)
- G J Moran
- Department of Emergency Medicine and Division of Infectious Diseases, UCLA School of Medicine, USA
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Wiedmann M, Liebert UG, Oesen U, Porst H, Wiese M, Schroeder S, Halm U, Mössner J, Berr F. Decreased immunogenicity of recombinant hepatitis B vaccine in chronic hepatitis C. Hepatology 2000; 31:230-4. [PMID: 10613751 DOI: 10.1002/hep.510310134] [Citation(s) in RCA: 117] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The immunogenicity of hepatitis B vaccine is unknown for patients with chronic hepatitis C, although hepatitis B vaccination is highly recommended in these patients. We therefore studied in a prospective open trial of 59 patients with chronic hepatitis C (mean age 42 years, hepatitis C for >10 years, Child-Pugh score < or = 5) and 58 healthy hospital staff persons the rate of nonresponse (anti-HBs <10 mIU/mL at 9 months) to recombinant hepatitis B vaccine (Gen H-B-Vax(R),10 microg intradeltoidal at month 0, 1, and 6). Nonresponse was observed in 18/59 (31%) patients with chronic hepatitis C and 5/58 (9%) healthy staff persons (P <.005) (vs. 7% in historical controls; P <.005), low response (anti-HBs 10-99 mIU/mL) in 19% of patients with chronic hepatitis C and 17% of staff persons. High-dose booster vaccination led to seroconversion in 12/15 (80%) of primary nonresponders. Primary nonresponse to HB vaccine was related neither to presence of early-stage liver cirrhosis nor magnitude of serum hepatitis C virus (HCV) RNA concentration, nor explained by the presence of human leukocyte antigen (HLA) types (B8 DR3, B44, DR7, DQ2) predisposing to low antibody response to hepatitis B surface antigen. The rate of primary nonresponse to the standard regimen of recombinant hepatitis B vaccine is surprisingly high in patients with longstanding chronic hepatitis C. Therefore, the antibody to HBV surface antigen (anti-HBs) titer response should be determined in these patients. Depending on the response titer, higher booster doses may be required to achieve and maintain seroprotection in these patients.
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Affiliation(s)
- M Wiedmann
- Department of Medicine II, University of Leipzig, Germany
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Kuo YH, Fabiani JN, Mohamed AS, Couetil JP, Lévy M, Gutmann L, Carpentier AF, Bélec L. Decreasing occupational risk related to blood-borne viruses in cardiovascular surgery in Paris, France. Ann Thorac Surg 1999; 68:2267-72. [PMID: 10617015 DOI: 10.1016/s0003-4975(99)01051-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
BACKGROUND Surgeons face the risk of patient-to-physician transmission of blood-borne viruses. This risk is related to the seroprevalence of the viruses in the patient population. METHODS The seroprevalence of the human immunodeficiency virus, hepatitis B virus, and hepatitis C virus were determined in cardiovascular patients at Hôpital Broussais in Paris, France, over a 5-year period (1994 to 1998). RESULTS Hepatitis C virus is the most prevalent virus in the patient population, whereas human immunodeficiency virus is the least frequent. The seroprevalence of hepatitis C virus and human immunodeficiency virus has decreased over time, whereas hepatitis B virus has remained constant. We apply the seroprevalence data to a mathematical model to estimate the occupational risk of seroconversion faced by surgeons over the length of their career. Our results show that the principal risk faced by the surgeon arises from hepatitis B virus and hepatitis C virus. The decreasing seroprevalence of the hepatitis C virus has resulted in a decrease in the occupational risk. CONCLUSIONS The probability of becoming infected with a blood-borne virus over the career of the surgeon is notable. The greatest occupational risk to the surgeon is from the hepatitis viruses and not HIV.
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Affiliation(s)
- Y H Kuo
- Laboratoire de Virologie, Service de Chirurgie Cardiovasculaire, Hôpital Broussais, Paris, France
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