1
|
Sheela Rani M, Dhanasekar S. Application of type-2 heptagonal fuzzy sets with multiple operators in multi-criteria decision-making for identifying risk factors of Zika virus. BMC Infect Dis 2025; 25:450. [PMID: 40169983 PMCID: PMC11963685 DOI: 10.1186/s12879-025-10741-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 03/03/2025] [Indexed: 04/03/2025] Open
Abstract
PURPOSE This study aims to identify and rank the key risk factors associated with the Zika virus by leveraging a novel multi-criteria decision-making (MCDM) framework based on type-2 heptagonal fuzzy sets. By integrating advanced aggregation operators, the framework effectively addresses uncertainties in expert assessments and enhances decision-making reliability. METHODS A robust MCDM approach was developed using type-2 heptagonal fuzzy sets, which provide a more nuanced representation of uncertainty compared to traditional fuzzy models. These sets were selected due to their superior ability to handle vague, imprecise, and subjective expert judgments, common challenges in epidemiological risk assessments. Arithmetic and geometric aggregation operators were employed to process fuzzy data effectively. To ensure comprehensive and reliable rankings, the framework incorporated both outranking methods and distance-based approaches, specifically TOPSIS and WASPAS. A sensitivity analysis was conducted to validate the stability of the rankings under varying conditions. RESULTS The proposed framework identified Z 3 (unprotected sexual activity) as the most critical risk factor with a score of 0.6717, followed by Z 8 (blood transfusions) at 0.5783, Z 10 (pregnancy) at 0.5753, Z 9 (mosquito bites) at 0.4917, and Z 7 (travel to endemic areas) at 0.4726. The rankings remained consistent across different MCDM methods (TOPSIS and WASPAS), demonstrating the robustness of the proposed approach. Pearson correlation analysis confirmed a strong agreement between methods, with correlation coefficients, reinforcing the reliability of the model. CONCLUSION This study introduces an advanced decision-support system for healthcare professionals to systematically identify and prioritize Zika virus risk factors. By leveraging type-2 heptagonal fuzzy sets, the framework effectively captures and processes uncertainty stemming from incomplete epidemiological data, imprecise expert assessments, and subjective linguistic evaluations. The consistency of rankings across multiple MCDM methods, along with sensitivity analysis confirming their stability, demonstrates the model's reliability. These findings provide a scientifically grounded tool for improving risk analysis and strategic public health interventions.
Collapse
Affiliation(s)
- M Sheela Rani
- Department of Mathematics, School of Advanced Sciences, Vellore Institute of Technology, Chennai, 600127, Tamilnadu, India
| | - S Dhanasekar
- Department of Mathematics, School of Advanced Sciences, Vellore Institute of Technology, Chennai, 600127, Tamilnadu, India.
| |
Collapse
|
2
|
dos Santos CR, dos Santos CGM, Couto-Lima D, Souza BS, Rahman RU, Dornelas Ribeiro M, Lima JBP, Martins AJ. Evaluation of Yellow Fever Virus Infection in Aedes aegypti Mosquitoes from Pakistan with Distinct Knockdown Resistance Genotypes. INSECTS 2024; 16:33. [PMID: 39859614 PMCID: PMC11765701 DOI: 10.3390/insects16010033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 11/28/2024] [Accepted: 12/05/2024] [Indexed: 01/27/2025]
Abstract
BACKGROUND Yellow fever (YF) is an acute hemorrhagic disease endemic to Africa and Latin America; however, no cases have been reported in Asian regions with high Aedes aegypti infestation. Factors such as environmental conditions and genetic variations in the yellow fever virus (YFV) strains and mosquito populations may explain this absence. Mosquito populations have undergone strong selective pressure owing to the excessive use of insecticides. This pressure has led to the spread of alterations, such as knockdown-resistant mutations (kdr), which, while conferring resistance to pyrethroids, also induce various physiological side effects in the insect. Therefore, it is important to investigate whether the presence of kdr mutations influences the infectivity of YFV mosquitoes. This study evaluated the susceptibility of Ae. aegypti from Pakistan with distinct kdr genotypes to different YFV strains under laboratory conditions. METHODS Ae. aegypti from a Pakistani colony were exposed to YFV strains (PR4408/2008 and ES504/2017) along with the Rockefeller strain. After 14 days, RNA and DNA were extracted for viral RNA detection (qPCR) and kdr genotyping (TaqMan qPCR and HRM for T1520I and F1534C SNPs). RESULTS Pakistani Ae. aegypti were orally susceptible to YFV, with infection rates of 83.7% (PR4408/2008) and 61.3% (ES504), respectively, similar to Rockefeller. Two kdr genotypes (II + CC and TI + FC) were identified, with no significant differences in viral infection or dissemination rates. CONCLUSIONS The Ae. aegypti population from Asia is capable of YFV infection and dissemination, regardless of kdr genotype.
Collapse
Affiliation(s)
- Carlucio Rocha dos Santos
- Laboratório de Biologia, Controlee Vigilância de InsetosVetores, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21040-360, RJ, Brazil (B.S.S.); (R.U.R.)
| | | | - Dinair Couto-Lima
- Laboratório de Mosquitos Transmissores de Hematozoários, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21040-360, RJ, Brazil
| | - Bárbara Silva Souza
- Laboratório de Biologia, Controlee Vigilância de InsetosVetores, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21040-360, RJ, Brazil (B.S.S.); (R.U.R.)
| | - Rafi Ur Rahman
- Laboratório de Biologia, Controlee Vigilância de InsetosVetores, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21040-360, RJ, Brazil (B.S.S.); (R.U.R.)
| | - Marcos Dornelas Ribeiro
- Instituto de Biologia do Exército, Divisão de Ensino e Pesquisa, Rio de Janeiro 20911-270, RJ, Brazil (M.D.R.)
| | - José Bento Pereira Lima
- Laboratório de Biologia, Controlee Vigilância de InsetosVetores, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21040-360, RJ, Brazil (B.S.S.); (R.U.R.)
| | - Ademir Jesus Martins
- Laboratório de Biologia, Controlee Vigilância de InsetosVetores, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro 21040-360, RJ, Brazil (B.S.S.); (R.U.R.)
- Instituto Nacional de Ciência e Tecnologia (INCT), Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
| |
Collapse
|
3
|
Vilibic-Cavlek T, Bogdanic M, Savic V, Hruskar Z, Barbic L, Stevanovic V, Antolasic L, Milasincic L, Sabadi D, Miletic G, Coric I, Mrzljak A, Listes E, Savini G. Diagnosis of West Nile virus infections: Evaluation of different laboratory methods. World J Virol 2024; 13:95986. [PMID: 39722752 PMCID: PMC11551685 DOI: 10.5501/wjv.v13.i4.95986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 08/14/2024] [Accepted: 08/27/2024] [Indexed: 10/18/2024] Open
Abstract
BACKGROUND The diagnosis of West Nile virus (WNV) is challenging due to short-term and low-level viremia, flavivirus cross-reactivity, and long immunoglobulin M (IgM) persistence. AIM To evaluate different methods for WNV detection [reverse transcription-polymerase chain reaction (RT-PCR), IgM/IgG antibodies, IgG avidity] in serum, cerebrospinal fluid (CSF), and urine samples of patients with confirmed WNV infection. METHODS The study included patients with confirmed WNV neuroinvasive infection (n = 62), asymptomatic WNV seropositive individuals (n = 22), and individuals with false-positive WNV IgM antibodies (n = 30). WNV RNA was detected using RT-PCR. A commercial ELISA was used to detect WNV IgM/IgG antibodies with confirmation of cross-reactive samples using a virus neutralization test (VNT). IgG-positive samples were tested for IgG avidity. RESULTS The WNV-RNA detection rates were significantly higher in the urine (54.5%)/serum (46.4%) than in CSF (32.2%). According to the sampling time, the WNV-RNA detection rates in urine collected within 7 days/8-14/≥ 15 days were 29.4/66.6/62.5% (P = 0.042). However, these differences were not observed in the CSF. The median RT-PCR cycle threshold values were significantly lower in urine (32.5, IQR = 28-34) than in CSF (34.5, IQR = 33-36). The frequency of positive WNV IgM and IgG significantly differed according to the sampling time in serum but not in CSF. Positive IgM/IgG antibodies were detected in 84.3/9.3% of serum samples collected within 7 days, 100/71.1% of samples collected 8-14, and 100% samples collected after ≥ 15 days. Recent WNV infection was confirmed by low/borderline avidity index (AI) in 13.6% of asymptomatic individuals. A correlation between ELISA and AI was strong negative for IgM and strong positive for IgG. No significant correlation between ELISA IgG and VNT was found. CONCLUSION The frequency of WNV RNA and antibody detection depends on the sampling time and type of clinical samples. IgG avidity could differentiate recent WNV infections from long-persisting IgM antibodies.
Collapse
Affiliation(s)
- Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, Zagreb 10000, Croatia
| | - Zeljka Hruskar
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine University of Zagreb, Zagreb 10000, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine University of Zagreb, Zagreb 10000, Croatia
| | - Ljiljana Antolasic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Ljiljana Milasincic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Dario Sabadi
- Department of Infectious Diseases, Clinical Hospital Center Osijek, Osijek 31000, Croatia
- Medical Faculty, Josip Juraj Strossmayer University of Osijek, Osijek 31000, Croatia
| | - Gorana Miletic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine University of Zagreb, Zagreb 10000, Croatia
| | - Ivona Coric
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine University of Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
| | - Eddy Listes
- Croatian Veterinary Institute, Veterinary Institute Split, Split 21000, Croatia
| | - Giovanni Savini
- OIE Reference Center for West Nile Disease, Istituto Zooprofilattico Sperimentale, G. Caporale, Teramo 64100, Italy
| |
Collapse
|
4
|
Cuevas-Juárez E, Liñan-Torres A, Hernández C, Kopylov M, Potter CS, Carragher B, Ramírez OT, Palomares LA. Mimotope discovery as a tool to design a vaccine against Zika and dengue viruses. Biotechnol Bioeng 2023; 120:2658-2671. [PMID: 37058415 DOI: 10.1002/bit.28392] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 03/18/2023] [Accepted: 03/20/2023] [Indexed: 04/15/2023]
Abstract
Vaccine development against dengue virus is challenging because of the antibody-dependent enhancement of infection (ADE), which causes severe disease. Consecutive infections by Zika (ZIKV) and/or dengue viruses (DENV), or vaccination can predispose to ADE. Current vaccines and vaccine candidates contain the complete envelope viral protein, with epitopes that can raise antibodies causing ADE. We used the envelope dimer epitope (EDE), which induces neutralizing antibodies that do not elicit ADE, to design a vaccine against both flaviviruses. However, EDE is a discontinuous quaternary epitope that cannot be isolated from the E protein without other epitopes. Utilizing phage display, we selected three peptides that mimic the EDE. Free mimotopes were disordered and did not elicit an immune response. After their display on adeno-associated virus (AAV) capsids (VLP), they recovered their structure and were recognized by an EDE-specific antibody. Characterization by cryo-EM and enzyme-linked immunosorbent assay confirmed the correct display of a mimotope on the surface of the AAV VLP and its recognition by the specific antibody. Immunization with the AAV VLP displaying one of the mimotopes induced antibodies that recognized ZIKV and DENV. This work provides the basis for developing a Zika and dengue virus vaccine candidate that will not induce ADE.
Collapse
Affiliation(s)
- Esmeralda Cuevas-Juárez
- Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos, Mexico
| | - Arturo Liñan-Torres
- Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos, Mexico
| | - Carolina Hernández
- National Center for In-situ Tomographic Ultramicroscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, New York, USA
| | - Mykhailo Kopylov
- National Center for In-situ Tomographic Ultramicroscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, New York, USA
| | - Clint S Potter
- National Center for In-situ Tomographic Ultramicroscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, New York, USA
| | - Bridget Carragher
- National Center for In-situ Tomographic Ultramicroscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, New York, USA
| | - Octavio T Ramírez
- Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos, Mexico
| | - Laura A Palomares
- Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos, Mexico
| |
Collapse
|
5
|
Abeygoonawardena H, Wijesinghe N, Navaratne V, Balasuriya A, Nguyen TTN, Moi ML, De Silva AD. Serological Evidence of Zika virus Circulation with Dengue and Chikungunya Infections in Sri Lanka from 2017. J Glob Infect Dis 2023; 15:113-120. [PMID: 37800085 PMCID: PMC10549900 DOI: 10.4103/jgid.jgid_195_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 03/23/2023] [Accepted: 06/20/2023] [Indexed: 10/07/2023] Open
Abstract
Introduction Arbovirus diseases remain a public health threat in Sri Lanka. Dengue is endemic and two outbreaks of chikungunya infections have been reported. There is limited data on Zika virus (ZIKV) infections in Sri Lanka, and this could be due to a lack of comprehensive ZIKV surveillance. Our aim was to determine the presence of antibodies to dengue, chikungunya, and Zika infections in adults from a suburban population in Sri Lanka. Methods A total of 149 healthy adult volunteers over 18 years of age (mean age: 43±14 years, males - 43%), with no prior diagnosed arboviral infections and no history of overseas travel, participated in the study. ELISA and neutralization assays were carried out to detect past dengue, chikungunya, or Zika infections. Results A total of 94.6% (141/149) of the participants demonstrated dengue IgG antibodies, 37.5% (56/149) were positive for chikungunya IgG, and 5.3% (8/149) were positive for anti-ZIKV IgG antibodies. Neutralization assays confirmed ZIKV-specific antibodies in 6.7% (10/149), when 40/149 of the participating population were tested. Conclusion This clearly demonstrated past ZIKV infections in this population. In addition, this study indicates that >90% of individuals had asymptomatic dengue but no serious symptoms. These results provide a cross-sectional view on the DENV, ZIKV, and CHIKV epidemic status and demonstrate a need for the implementation of enhanced surveillance and more effective measures against the spread of these arbovirus diseases.
Collapse
Affiliation(s)
- Harshi Abeygoonawardena
- Department of Clinical Sciences, General Sir John Kotelawala Defence University, Ratmalana, Sri Lanka
| | - Namal Wijesinghe
- Department of Clinical Sciences, General Sir John Kotelawala Defence University, Ratmalana, Sri Lanka
| | - Varuna Navaratne
- Department of Paraclinical Sciences, Faculty of Medicine, General Sir John Kotelawala Defence University, Ratmalana, Sri Lanka
| | - Aindralal Balasuriya
- Department of Paraclinical Sciences, Faculty of Medicine, General Sir John Kotelawala Defence University, Ratmalana, Sri Lanka
| | - Thi Thanh Ngan Nguyen
- Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
| | - Meng Ling Moi
- Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
- Department of Developmental Medical Sciences, School of International Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Aruna Dharshan De Silva
- Department of Paraclinical Sciences, Faculty of Medicine, General Sir John Kotelawala Defence University, Ratmalana, Sri Lanka
| |
Collapse
|
6
|
Kim IJ, Tighe MP, Clark MJ, Gromowski GD, Lanthier PA, Travis KL, Bernacki DT, Cookenham TS, Lanzer KG, Szaba FM, Tamhankar MA, Ross CN, Tardif SD, Layne-Colon D, Dick EJ, Gonzalez O, Giraldo Giraldo MI, Patterson JL, Blackman MA. Impact of prior dengue virus infection on Zika virus infection during pregnancy in marmosets. Sci Transl Med 2023; 15:eabq6517. [PMID: 37285402 DOI: 10.1126/scitranslmed.abq6517] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 05/18/2023] [Indexed: 06/09/2023]
Abstract
Zika virus (ZIKV) infection during pregnancy causes severe developmental defects in newborns, termed congenital Zika syndrome (CZS). Factors contributing to a surge in ZIKV-associated CZS are poorly understood. One possibility is that ZIKV may exploit the antibody-dependent enhancement of infection mechanism, mediated by cross-reactive antibodies from prior dengue virus (DENV) infection, which may exacerbate ZIKV infection during pregnancy. In this study, we investigated the impact of prior DENV infection or no DENV infection on ZIKV pathogenesis during pregnancy in a total of four female common marmosets with five or six fetuses per group. The results showed that negative-sense viral RNA copies increased in the placental and fetal tissues of DENV-immune dams but not in DENV-naïve dams. In addition, viral proteins were prevalent in endothelial cells, macrophages, and neonatal Fc receptor-expressing cells in the placental trabeculae and in neuronal cells in the brains of fetuses from DENV-immune dams. DENV-immune marmosets maintained high titers of cross-reactive ZIKV-binding antibodies that were poorly neutralizing, raising the possibility that these antibodies might be involved in the exacerbation of ZIKV infection. These findings need to be verified in a larger study, and the mechanism involved in the exacerbation of ZIKV infection in DENV-immune marmosets needs further investigation. However, the results suggest a potential negative impact of preexisting DENV immunity on subsequent ZIKV infection during pregnancy in vivo.
Collapse
Affiliation(s)
- In-Jeong Kim
- Trudeau Institute Inc., Saranac Lake, NY 12983, USA
| | | | | | - Gregory D Gromowski
- Viral Diseases Branch, Center of Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | | | | | | | | | | | | | - Manasi A Tamhankar
- Southwest National Primate Center, Texas Biomedical Research Institute, San Antonio, TX 78227, USA
| | - Corrina N Ross
- Southwest National Primate Center, Texas Biomedical Research Institute, San Antonio, TX 78227, USA
| | - Suzette D Tardif
- Southwest National Primate Center, Texas Biomedical Research Institute, San Antonio, TX 78227, USA
| | - Donna Layne-Colon
- Southwest National Primate Center, Texas Biomedical Research Institute, San Antonio, TX 78227, USA
| | - Edward J Dick
- Southwest National Primate Center, Texas Biomedical Research Institute, San Antonio, TX 78227, USA
| | - Olga Gonzalez
- Southwest National Primate Center, Texas Biomedical Research Institute, San Antonio, TX 78227, USA
| | - Maria I Giraldo Giraldo
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
| | - Jean L Patterson
- Southwest National Primate Center, Texas Biomedical Research Institute, San Antonio, TX 78227, USA
| | | |
Collapse
|
7
|
Boonyasuppayakorn S, Saelee T, Huynh TNT, Hairani R, Hengphasatporn K, Loeanurit N, Cao V, Vibulakhaophan V, Siripitakpong P, Kaur P, Chu JJH, Tunghirun C, Choksupmanee O, Chimnaronk S, Shigeta Y, Rungrotmongkol T, Chavasiri W. The 8-bromobaicalein inhibited the replication of dengue, and Zika viruses and targeted the dengue polymerase. Sci Rep 2023; 13:4891. [PMID: 36966240 PMCID: PMC10039358 DOI: 10.1038/s41598-023-32049-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/21/2023] [Indexed: 03/27/2023] Open
Abstract
Dengue and Zika viruses are mosquito-borne flaviviruses burdening millions every year with hemorrhagic fever and neurological symptoms. Baicalein was previously reported as a potential anti-flaviviral candidate and halogenation of flavones and flavanones potentiated their antiviral efficacies. Here, we reported that a chemically modified 8-bromobaicalein effectively inhibited all dengue serotypes and Zika viruses at 0.66-0.88 micromolar in cell-based system. The compound bound to dengue serotype 2 conserved pocket and inhibited the dengue RdRp activity with 6.93 fold more than the original baicalein. Moreover, the compound was mildly toxic against infant and adult C57BL/6 mice despite administering continuously for 7 days. Therefore, the 8-bromobaicalein should be investigated further in pharmacokinetics and efficacy in an animal model.
Collapse
Affiliation(s)
- Siwaporn Boonyasuppayakorn
- Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
| | - Thanaphon Saelee
- Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Thao Nguyen Thanh Huynh
- Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Rita Hairani
- Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Kowit Hengphasatporn
- Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan
| | - Naphat Loeanurit
- Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
- Graduate School, Interdisciplinary Program in Microbiology, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Van Cao
- Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
- Graduate School, Interdisciplinary Program in Microbiology, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Vipanee Vibulakhaophan
- Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
- Department of Biology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Panattida Siripitakpong
- Center of Excellence in Biocatalyst and Sustainable Biotechnology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Parveen Kaur
- Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore
| | - Justin Jang Hann Chu
- Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore
- Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- NUS Medicine BSL3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore, Singapore
| | - Chairat Tunghirun
- The Laboratory of RNA Biology, Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakhon Pathom, 73170, Thailand
| | - Opas Choksupmanee
- The Laboratory of RNA Biology, Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakhon Pathom, 73170, Thailand
| | - Sarin Chimnaronk
- The Laboratory of RNA Biology, Institute of Molecular Biosciences, Mahidol University, Salaya Campus, Nakhon Pathom, 73170, Thailand
| | - Yasuteru Shigeta
- Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan
| | - Thanyada Rungrotmongkol
- Center of Excellence in Biocatalyst and Sustainable Biotechnology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
- Program in Bioinformatics and Computational Biology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Warinthorn Chavasiri
- Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| |
Collapse
|
8
|
Tricou V, Essink B, Ervin JE, Turner M, Escudero I, Rauscher M, Brose M, Lefevre I, Borkowski A, Wallace D. Immunogenicity and safety of concomitant and sequential administration of yellow fever YF-17D vaccine and tetravalent dengue vaccine candidate TAK-003: A phase 3 randomized, controlled study. PLoS Negl Trop Dis 2023; 17:e0011124. [PMID: 36888687 PMCID: PMC9994689 DOI: 10.1371/journal.pntd.0011124] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 01/29/2023] [Indexed: 03/09/2023] Open
Abstract
BACKGROUND Yellow fever (YF) vaccination is often mandatory for travelers to YF-endemic areas. The areas with risk of YF partially overlap with those of dengue, for which there is currently no recommended vaccine available for dengue-naïve individuals. This phase 3 study assessed the immunogenicity and safety of concomitant and sequential administration of YF (YF-17D) and tetravalent dengue (TAK-003) vaccines in healthy adults aged 18-60 years living in areas of the US non-endemic for either virus. METHODS Participants were randomized 1:1:1 to receive the following vaccinations at Months 0, 3, and 6, respectively: YF-17D+placebo, TAK-003, and TAK-003 (Group 1); TAK-003+placebo, TAK-003, and YF-17D (Group 2); or YF-17D+TAK-003, TAK-003, and placebo (Group 3). The primary objective was to demonstrate non-inferiority (upper bound of 95% confidence interval [UB95%CI] of difference <5%) of YF seroprotection rate one month following concomitant administration of YF-17D and TAK-003 (Group 3) compared with YF-17D plus placebo (Group 1). The secondary objectives included demonstration of non-inferiority of YF and dengue geometric mean titers (GMTs) (UB95%CI for GMT ratio <2.0), and safety. RESULTS 900 adults were randomized. YF seroprotection rates one month post-YF-17D (Month 1) were 99.5% and 99.1% in Group 1 and 3, respectively, and non-inferiority was demonstrated (UB95%CI = 2.69% i.e. <5%). Non-inferiority was also demonstrated for GMTs against YF one month post-YF-17D, and against DENV-2, -3, and -4 (UB95%CI <2), but not DENV-1 (UB95%CI: 2.22), one month post-second TAK-003 vaccination. Adverse event rates following TAK-003 were consistent with previous results, and no important safety risks were identified. CONCLUSIONS In this study, YF-17D vaccine and TAK-003 were immunogenic and well tolerated when sequentially or concomitantly administered. The non-inferiority of immune responses to YF-17D and TAK-003 was demonstrated for concomitant administration of the 2 vaccines compared to separate vaccination, except against DENV-1 but with GMTs similar to those observed in other TAK-003 trials. TRIAL REGISTRATION ClinicalTrials.gov identified: NCT03342898.
Collapse
Affiliation(s)
- Vianney Tricou
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
- * E-mail:
| | - Brandon Essink
- Meridian Clinical Research, Omaha, Nebraska, United States of America
| | - John E. Ervin
- Center for Pharmaceutical Research Inc, Kansas City, Missouri, United States of America
| | - Mark Turner
- Advanced Clinical Research, Boise, Idaho, United States of America
| | | | | | - Manja Brose
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
| | - Inge Lefevre
- Takeda Pharmaceuticals International AG, Zurich, Switzerland
| | | | - Derek Wallace
- Takeda Vaccines Inc., Boston, Massachusetts, United States of America
| |
Collapse
|
9
|
Low Immune Cross-Reactivity between West Nile Virus and a Zika Virus Vaccine Based on Modified Vaccinia Virus Ankara. Pharmaceuticals (Basel) 2022; 15:ph15030354. [PMID: 35337151 PMCID: PMC8955905 DOI: 10.3390/ph15030354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/04/2022] [Accepted: 03/12/2022] [Indexed: 02/01/2023] Open
Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus whose infection in pregnant women is associated with a spectrum of birth defects, which are together referred as Congenital Zika Syndrome. In addition, ZIKV can also induce Guillain–Barré syndrome, which is an autoimmune disease with neurological symptoms. The recent description of the first local infections of ZIKV in the European continent together with the expansion of one of its potential vectors, the Asian tiger mosquito (Aedes albopictus), invite us to be prepared for future outbreaks of ZIKV in this geographical region. However, the antigenic similarities of ZIKV with other flaviviruses can lead to an immune cross-reactivity with other circulating flaviviruses inducing, in some cases, flavivirus-disease exacerbation by antibody-dependent enhancement (ADE) of infection, which is a major concern for ZIKV vaccine development. Until now, West Nile virus (WNV) is the main medically relevant flavivirus circulating in the Mediterranean Basin. Therefore, anticipating the potential scenario of emergency vaccination against ZIKV in areas of Europe where WNV is endemic, in this investigation, we have evaluated the cross-reactivity between WNV and our previously developed ZIKV vaccine candidate based on modified vaccinia virus Ankara (MVA) vector expressing ZIKV structural proteins (MVA-ZIKV). To this end, mice were first immunized with MVA-ZIKV, subsequently challenged with WNV, and then, the ZIKV- and WNV-specific immune responses and protection against WNV were evaluated. Our results indicate low cross-reactivity between the MVA-ZIKV vaccine candidate and WNV and absence of ADE, supporting the safety of this ZIKV vaccine candidate in areas where the circulation of WNV is endemic.
Collapse
|
10
|
Gehrke F, Cardoso Gois K, da Costa Alves Aguiar Reis B, Zorello Laporta G, Affonso Fonseca FL. Dengue 2 serotype and yellow fever coinfection. Access Microbiol 2022; 3:000300. [PMID: 35024560 PMCID: PMC8749146 DOI: 10.1099/acmi.0.000300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 10/31/2021] [Indexed: 01/02/2023] Open
Abstract
Case Presentation Arboviruses primarily consist of RNA, which favours greater genetic plasticity, with a higher frequency of mutations that allow the virus to adapt to different hosts. The initial symptomatology is nonspecific, in that the patient can present fever, myalgia, arthralgia, rash and headache. This makes a clinical diagnosis using laboratory tests difficult and time-consuming. In Brazil, the main arboviruses involved in epidemics belong to the family Flaviviridae. The patient in this case is from the municipality of São Bernardo do Campo, an area endemic for arboviruses. He presented symptoms of fever, myalgia and headache. Results The multiplex assay for arboviruses detected genetic material from the dengue 2 and yellow fever viruses. Conclusion This result confirms the importance of molecular tests showing high sensitivity and specificity that can assist clinical diagnosis, particularly in endemic areas during periods of outbreak for other arboviruses, like the epidemiological picture in Brazil in 2018, when significant co-circulation of dengue virus and yellow fever virus occurred. The presence of co-circulating arboviruses increases the chance of coinfection and demonstrates the importance of differential diagnosis.
Collapse
Affiliation(s)
- Flávia Gehrke
- Programa de Pós Graduação em Ciências da Saúde, Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE), São Paulo, Brazil.,Patologia, Centro Universitário FMABC, Santo André, São Paulo, Brazil.,Programa de Pós Graduação em Ciências da Saúde, Centro Universitário FMABC, São Paulo, Santo André, Brazil.,Present address: Programa de Pós Graduação em Ciências da Saúde, Centro Universitário FMABC, São Paulo, Santo André, Brazil
| | - Katharyna Cardoso Gois
- Programa de Pós Graduação em Ciências da Saúde, Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE), São Paulo, Brazil
| | | | - Gabriel Zorello Laporta
- Programa de Pós Graduação em Ciências da Saúde, Centro Universitário FMABC, São Paulo, Santo André, Brazil
| | - Fernando Luiz Affonso Fonseca
- Programa de Pós Graduação em Ciências da Saúde, Centro Universitário FMABC, São Paulo, Santo André, Brazil.,Laboratório de Análises Clínicas, FMABC-Centro Universitário Saúde ABC, Santo André, São Paulo, Brazil.,Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo (UNIFESP), Diadema, São Paulo, Brazil
| |
Collapse
|
11
|
Santos JPCD, Albuquerque HG, Siqueira ASP, Praça HLF, Pereira LV, Tavares ADM, Gusmão EVV, Bruno PRDA, Barcellos C, Carvalho MDS, Sabroza PC, Honório NA. ARBOALVO: estratificação territorial para definição de áreas de pronta resposta para vigilância e controle de arboviroses urbanas em tempo oportuno. CAD SAUDE PUBLICA 2022; 38:e00110121. [DOI: 10.1590/0102-311x00110121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 10/22/2021] [Indexed: 11/21/2022] Open
Abstract
O objetivo deste trabalho foi apresentar a proposta metodológica denominada de “Pronta Resposta” modelada nas cidades de Belo Horizonte (Minas Gerais) e Natal (Rio Grande do Norte), Brasil. A metodologia visa identificar e delimitar áreas prioritárias para o direcionamento das ações de vigilância em tempo oportuno, buscando a redução da intensidade e velocidade da dispersão de epidemias em áreas urbanas endêmicas. Para tanto, a metodologia utiliza três variáveis, que representam as causas necessárias para a produção e reprodução da dengue: casos notificados (vírus), ovos de Aedes (vetor) e população (hospedeiro). Trata-se de um estudo ecológico que utilizou os dados dos três planos de informações agregados em escalas temporais e espaciais mais finas, de três a quatro semanas e grades de 400 a 600 metros respectivamente. As áreas de pronta resposta foram definidas por meio de análise estatística de varredura Scan, com definição de clusters espaciais simultâneos para os três planos por meio do programa SaTScan. Os resultados observados foram: na cidade de Natal, as áreas definidas como pronta resposta ocuparam em média 15,2% do território do município e concentraram 67,77% dos casos de dengue do período posterior ao utilizado na delimitação das áreas de pronta resposta, e em Belo Horizonte, os números observados foram de 64,16% dos casos em 23,23% do território. Esses resultados foram obtidos em duas cidades com realidades socioambientais e geográficas diferentes e com perfis epidemiológicos também distintos, apontando que a metodologia pode ser aplicada em diferentes realidades urbanas, criando a possibilidade de os programas de controle atuarem em porções reduzidas do território e impactar num alto percentual de casos em tempo oportuno.
Collapse
|
12
|
Falconi-Agapito F, Kerkhof K, Merino X, Michiels J, Van Esbroeck M, Bartholomeeusen K, Talledo M, Ariën KK. Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection. Front Immunol 2021; 12:686691. [PMID: 34290707 PMCID: PMC8289389 DOI: 10.3389/fimmu.2021.686691] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Accepted: 06/17/2021] [Indexed: 12/22/2022] Open
Abstract
Dengue is a major public health problem in tropical and sub-tropical regions worldwide. Since the Zika epidemic and the increased co-circulation of other arboviruses, the serology-based diagnosis of dengue has become more problematic due to the high antigenic resemblance, especially among the flavivirus family. Therefore, a more comprehensive understanding of the diversity, specificity and temporal evolution of the antibody response following dengue infection is needed. In order to close this knowledge gap, we used a high-density peptide microarray of 9,072 linear peptides covering the entire proteome diversity of dengue, Zika, yellow fever and chikungunya viruses. The IgM and IgG antibody responses were measured against the designed microarray in symptomatic dengue infected individuals from an arbovirus endemic area in Peru and in overseas travelers returning to Belgium, as representatives of multiple-exposed and primary infections, respectively. Serum samples were collected longitudinally across four time points over the period of six months in Peru and over two time points in travelers. We show that epitopes eliciting the strongest flavivirus cross-reactive antibodies, in both primary and secondary infections were concentrated in the capsid, E, NS1, NS3 and NS5 proteins. The IgG antibody responses against NS1 and NS3 followed a rise-and-fall pattern, with peak titers between two to four weeks after onset of illness. The response to the E and NS5 proteins increased rapidly in the acute phase and was maintained at stable levels until at least 6 months after illness. A more scattered IgM antibody reactivity across the viral proteome was observed in the acute phase of the disease and that persisted through the 6-month window. The magnitude, breadth (i.e. number of unique epitopes targeted) and depth (i.e. number of epitope variants recognized) of the IgG response was higher in secondary infections compared to primary infections. For IgM antibodies, the magnitude of the response was higher in primary infected individuals whereas the breadth and depth of the response was lower in this group compared with the endemic subjects. Finally, through this arboviral proteome-wide epitope mapping, we were able to identify IgM and IgG dengue-specific epitopes which can be useful serological markers for dengue diagnosis and serostatus determination.
Collapse
Affiliation(s)
- Francesca Falconi-Agapito
- Department of Biomedical Sciences, Unit of Virology, Institute of Tropical Medicine, Antwerp, Belgium
- Virology Unit, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Karen Kerkhof
- Department of Biomedical Sciences, Unit of Virology, Institute of Tropical Medicine, Antwerp, Belgium
| | - Xiomara Merino
- Virology Unit, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Johan Michiels
- Department of Biomedical Sciences, Unit of Virology, Institute of Tropical Medicine, Antwerp, Belgium
| | - Marjan Van Esbroeck
- Department of Clinical Sciences, National Reference Center for Arboviruses, Institute of Tropical Medicine, Antwerp, Belgium
| | - Koen Bartholomeeusen
- Department of Biomedical Sciences, Unit of Virology, Institute of Tropical Medicine, Antwerp, Belgium
| | - Michael Talledo
- Virology Unit, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Kevin K. Ariën
- Department of Biomedical Sciences, Unit of Virology, Institute of Tropical Medicine, Antwerp, Belgium
- Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| |
Collapse
|
13
|
Lim JK, Carabali M, Edwards T, Barro A, Lee JS, Dahourou D, Lee KS, Nikiema T, Shin MY, Bonnet E, Kagone T, Kaba L, Namkung S, Somé PA, Yang JS, Ridde V, Yoon IK, Alexander N, Seydou Y. Estimating the Force of Infection for Dengue Virus Using Repeated Serosurveys, Ouagadougou, Burkina Faso. Emerg Infect Dis 2021; 27:130-139. [PMID: 33350906 PMCID: PMC7774580 DOI: 10.3201/eid2701.191650] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Because of limited data on dengue virus in Burkina Faso, we conducted 4 consecutive age-stratified longitudinal serologic surveys, ≈6 months apart, among persons 1–55 years of age, during June 2015–March 2017, which included a 2016 outbreak. The seroconversion rate before the serosurvey enrollment was estimated by binomial regression, taking age as the duration of exposure, and assuming constant force of infection (FOI) over age and calendar time. We calculated FOI between consecutive surveys and rate ratios for potentially associated characteristics based on seroconversion using the duration of intervals. Among 2,897 persons at enrollment, 66.3% were IgG-positive, and estimated annual FOI was 5.95%. Of 1,269 enrollees participating in all 4 serosurveys, 438 were IgG-negative at enrollment. The annualized FOI ranged from 10% to 20% (during the 2016 outbreak). Overall, we observed high FOI for dengue. These results could support decision-making about control and preventive measures for dengue.
Collapse
|
14
|
Lying in wait: the resurgence of dengue virus after the Zika epidemic in Brazil. Nat Commun 2021; 12:2619. [PMID: 33976183 PMCID: PMC8113494 DOI: 10.1038/s41467-021-22921-7] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 04/07/2021] [Indexed: 12/19/2022] Open
Abstract
After the Zika virus (ZIKV) epidemic in the Americas in 2016, both Zika and dengue incidence declined to record lows in many countries in 2017–2018, but in 2019 dengue resurged in Brazil, causing ~2.1 million cases. In this study we use epidemiological, climatological and genomic data to investigate dengue dynamics in recent years in Brazil. First, we estimate dengue virus force of infection (FOI) and model mosquito-borne transmission suitability since the early 2000s. Our estimates reveal that DENV transmission was low in 2017–2018, despite conditions being suitable for viral spread. Our study also shows a marked decline in dengue susceptibility between 2002 and 2019, which could explain the synchronous decline of dengue in the country, partially as a result of protective immunity from prior ZIKV and/or DENV infections. Furthermore, we performed phylogeographic analyses using 69 newly sequenced genomes of dengue virus serotype 1 and 2 from Brazil, and found that the outbreaks in 2018–2019 were caused by local DENV lineages that persisted for 5–10 years, circulating cryptically before and after the Zika epidemic. We hypothesize that DENV lineages may circulate at low transmission levels for many years, until local conditions are suitable for higher transmission, when they cause major outbreaks. Zika and dengue incidence in the Americas declined in 2017–2018, but dengue resurged in 2019 in Brazil. This study uses epidemiological, climatological and genomic data to show that the decline of dengue may be explained by protective immunity from pre-exposure to ZIKV and/or DENV in prior years.
Collapse
|
15
|
Xu L, Ma Z, Li Y, Pang Z, Xiao S. Antibody dependent enhancement: Unavoidable problems in vaccine development. Adv Immunol 2021; 151:99-133. [PMID: 34656289 PMCID: PMC8438590 DOI: 10.1016/bs.ai.2021.08.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
In some cases, antibodies can enhance virus entry and replication in cells. This phenomenon is called antibody-dependent infection enhancement (ADE). ADE not only promotes the virus to be recognized by the target cell and enters the target cell, but also affects the signal transmission in the target cell. Early formalin-inactivated virus vaccines such as aluminum adjuvants (RSV and measles) have been shown to induce ADE. Although there is no direct evidence that there is ADE in COVID-19, this potential risk is a huge challenge for prevention and vaccine development. This article focuses on the virus-induced ADE phenomenon and its molecular mechanism. It also summarizes various attempts in vaccine research and development to eliminate the ADE phenomenon, and proposes to avoid ADE in vaccine development from the perspective of antigens and adjuvants.
Collapse
|
16
|
Post-Vaccination Yellow Fever Antiserum Reduces Zika Virus in Embryoid Bodies When Placental Cells are Present. Vaccines (Basel) 2020; 8:vaccines8040752. [PMID: 33322247 PMCID: PMC7768546 DOI: 10.3390/vaccines8040752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/09/2020] [Accepted: 11/29/2020] [Indexed: 11/18/2022] Open
Abstract
Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody-mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for the in vitro recapitulation of the maternal–fetal interface. This study utilized a transwell assay, which was a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body, to replicate the maternal–fetal axis. To determine if cross-reactive YFV vaccine antibodies impacted the pathogenesis of ZIKV across the maternal–fetal axis, syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine antisera, and the viral load was measured 72 h post-inoculation. Here, we report that BeWo and HUVEC cells were permissive to ZIKV and that the impact of YFV post-vaccination antibodies on ZIKV replication was cell line-dependent. Embryoid bodies were also permissive to ZIKV, and the presence of YFV antibodies collected 4–14 months post-vaccination reduced ZIKV infection when placental cells were present. However, when directly infected with ZIKV, the embryoid bodies displayed significantly increased viral loads in the presence of YFV antiserum taken 30 days post-vaccination. The data show that each of the cell lines and EBs have a unique response to ZIKV complexed with post-vaccination serum, suggesting there may be cell-specific mechanisms that impact congenital ZIKV infections. Since ZIKV infections can cause severe congenital syndromes, it is crucial to understand any potential enhancement or protection offered from cross-reactive, post-vaccination antibodies.
Collapse
|
17
|
Bordallo B, Bellas M, Cortez AF, Vieira M, Pinheiro M. Severe COVID-19: what have we learned with the immunopathogenesis? Adv Rheumatol 2020; 60:50. [PMID: 32962761 PMCID: PMC7506814 DOI: 10.1186/s42358-020-00151-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 09/07/2020] [Indexed: 01/08/2023] Open
Abstract
The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself.Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena.Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS-CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.
Collapse
Affiliation(s)
- Bruno Bordallo
- Departament of Internal Medicine / Emergence, Hospital Universitário Antônio Pedro / Univesidade Federal Fluminense, Niterói, RJ, Brazil.
| | - Mozart Bellas
- Departament of Internal Medicine / Emergence, Hospital Universitário Antônio Pedro / Universidade Federal Fluminense, Niterói, RJ, Brazil
| | - Arthur Fernandes Cortez
- Hospital Universitário Gaffré e Guinle / Universidade Federal do Estado do Rio de Janeiro, Internal Medicine Departament, Rio de Janeiro, RJ, Brazil
| | - Matheus Vieira
- Departament of Internal Medicine, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, RJ, Brazil
| | - Marcelo Pinheiro
- Departament of Rheumatology, Universidade Federal de São Paulo, Sao Paulo, SP, Brazil
| |
Collapse
|
18
|
Rapid decline of Zika virus NS1 antigen-specific antibody responses, northeastern Brazil. Virus Genes 2020; 56:632-637. [PMID: 32542479 PMCID: PMC7294518 DOI: 10.1007/s11262-020-01772-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 05/22/2020] [Indexed: 01/08/2023]
Abstract
Zika virus (ZIKV) is a positive-stranded RNA virus within the Flaviviridae family. After decades of circulation in Asia, ZIKV was introduced to Brazil in 2014–2015, associated with a rise in congenital malformations. Unlike the genetically related dengue virus (DENV), ZIKV constitutes only one serotype. Although assumed that ZIKV infection may engender lifelong immunity, the long-term kinetics of ZIKV antibody responses are unclear. We assessed long-term kinetics of ZIKV NS1-IgG response in 144 individuals from 3 different subpopulations: HIV patients, tuberculosis patients and healthy individuals first tested in 2016 and retested 1.5–2 years after the 2015–2016 ZIKV epidemic in Salvador de Bahia, Brazil, using a widely distributed NS1-based commercial ELISA. The seropositivity in 2016 reached 59.0% (85/144, 95% confidence interval (CI) 50.7–66.7%), and decreased to 38.6% (56/144, CI 31.3–47.0%) 1.5–2 years later. In addition, the median ZIKV NS1-ELISA reactivity for individuals that remained positive in both timepoints significantly decreased from a ratio of 4.4 (95% CI 3.8–5.0) to 1.6 (95% CI 1.6–1.9) over the 2-year interval (Z: − 6.1; p < 0.001) irrespective of the subpopulation analyzed. Initial 2016 DENV antibody response was non-significant between groups, suggesting comparable DENV background. The high 20.6% seroreversion suggest that widely used serologic tests may fail to account a considerable proportion of past ZIKV infections in flavivirus endemic countries. In addition, ZIKV immunity might be shorter-lived than previously thought, which may contribute to local ZIKV resurgence once individual immune responses wane sufficiently to reduce community protective immunity in addition to birth and migration.
Collapse
|
19
|
Cárdenas DM, Jaimes MA, Vega LD, Oliveros NL, Soto JA, Chía CR, Osorio JE, Ciuoderis KA. Immunological Memory to Zika Virus in a University Community in Colombia, South America. AN ACAD BRAS CIENC 2020; 92:e20190883. [PMID: 32491129 DOI: 10.1590/0001-3765202020190883] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 11/18/2019] [Indexed: 11/22/2022] Open
Abstract
Zika virus appeared in South America in 2015, generating alarm worldwide as it causes microcephaly and autoimmunity. This study aims to determine the serological footprint of the incoming epidemic in a student community and to characterize the memory functional cell response during post convalescence. In a cross-sectional study, Zika-specific IgG using LIA immunoassay was found in 328 university students (CI=95%), while in the second phase, the functional cellular memory response for IFN-γ and IL-2 was quantified using post-stimulus ELISpot with inactivated virus, starting with individuals seropositive for Zika and control individuals (seropositive only for Dengue and seronegative for Zika-Dengue). Depending on the antigen used, memory humoral response (IgG) against Zika Virus was observed in >60% of the population; seropositivity for NS1 was 21.1% higher than E antigen with high intensity. The analysis of cell functionality in 22 individuals seropositive for Zika virus revealed either IFN-γ+ or IL-2+ cells in 86.3% of cases (Th1 profile), presenting multifunctionality in 50% (11 individuals), 64% of which presented> 6 SFC/104 PBMCs (>600 SFC/106 PBMC), reflecting memory circulating cells. A good agreement (Kappa= 0.754) was observed between the coexistence of both cellular and humoral responses but not in their intensity.
Collapse
Affiliation(s)
- Denny M Cárdenas
- Faculty of Health Sciences, Universidad de Santander, Cucuta, Colombia
| | - Miguel A Jaimes
- Faculty of Health Sciences, Universidad de Santander, Cucuta, Colombia
| | - Leidy D Vega
- Faculty of Health Sciences, Universidad de Santander, Cucuta, Colombia
| | | | - Javier A Soto
- Faculty of Health Sciences, Universidad de Santander, Cucuta, Colombia
| | - Claudia R Chía
- Faculty of Health Sciences, Universidad de Santander, Cucuta, Colombia
| | - Jorge E Osorio
- Department of Pathobiological Sciences, University of Wisconsin, Madison, USA
| | - Karl A Ciuoderis
- Center for Research and Surveillance of Tropical and Infectious Diseases, Universidad Nacional de Colombia, Medellin, Colombia
| |
Collapse
|
20
|
Lega S, Naviglio S, Volpi S, Tommasini A. Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19. Vaccines (Basel) 2020; 8:E224. [PMID: 32423059 PMCID: PMC7349555 DOI: 10.3390/vaccines8020224] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 05/10/2020] [Accepted: 05/11/2020] [Indexed: 01/08/2023] Open
Abstract
As the outbreak of the new coronavirus (SARS-CoV-2) infection is spreading globally, great effort is being made to understand the disease pathogenesis and host factors that predispose to disease progression in an attempt to find a window of opportunity for intervention. In addition to the direct cytopathic effect of the virus, the host hyper-inflammatory response has emerged as a key factor in determining disease severity and mortality. Accumulating clinical observations raised hypotheses to explain why some patients develop more severe disease while others only manifest mild or no symptoms. So far, Covid-19 management remains mainly supportive. However, many researches are underway to clarify the role of antiviral and immunomodulating drugs in changing morbidity and mortality in patients who become severely ill. This review summarizes the current state of knowledge on the interaction between SARS-CoV-2 and the host immune system and discusses recent findings on proposed pharmacologic treatments.
Collapse
Affiliation(s)
- Sara Lega
- Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy; (S.L.); (A.T.)
| | - Samuele Naviglio
- Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy; (S.L.); (A.T.)
| | - Stefano Volpi
- Center for Autoinflammatory Diseases and Immunodeficiency, IRCCS Istituto Giannina Gaslini and Università degli Studi di Genova, 16147 Genova, Italy;
| | - Alberto Tommasini
- Institute for Maternal and Child Health IRCCS Burlo Garofolo, 34137 Trieste, Italy; (S.L.); (A.T.)
- Department of Medicine, Surgery and Health Sciences, University of Trieste, 34137 Trieste, Italy
| |
Collapse
|
21
|
Nguyen CT, Moi ML, Le TQM, Nguyen TTT, Vu TBH, Nguyen HT, Pham TTH, Le THT, Nguyen LMH, Phu Ly MH, Ng CFS, Takemura T, Morita K, Hasebe F. Prevalence of Zika virus neutralizing antibodies in healthy adults in Vietnam during and after the Zika virus epidemic season: a longitudinal population-based survey. BMC Infect Dis 2020; 20:332. [PMID: 32393198 PMCID: PMC7216417 DOI: 10.1186/s12879-020-05042-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 04/16/2020] [Indexed: 12/24/2022] Open
Abstract
Background Between 2016 and 2019, 265 cases of Zika virus (ZIKV) infection were reported in Vietnam, predominantly in southern Vietnam. In 2016, a case of ZIKV-associated microcephaly was confirmed in the Central Highlands, and several members of the infant’s family were confirmed to be infected with ZIKV. The study aims to determine the level of immunity to ZIKV in the general population of the ZIKV epidemic region. Methods A total of 879 serum samples were collected from 801 participants between January 2017 and July 2018, during and after the ZIKV epidemic in Vietnam. The samples were tested for anti-ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG), and anti-dengue virus (DENV) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Plaque-reduction neutralization test (PRNT) for ZIKV was performed on all samples, and for DENV on the samples that ZIKV neutralizing antibody positive. Results A total of 83 (10.3%) participants had anti-ZIKV IgM. Of the 83, 6 were confirmed to be ZIKV antibodies positive using PRNT and anti-ZIKV IgG ELISA. Of the 718 participants who were anti-ZIKV IgM negative, a further 3 cases were confirmed as positive for antibodies against ZIKV. Of the 9 participants with ZIKV infection, 5 lived in the same village as the infant with ZIKV-associated microcephaly and the other 4 lived in 2 neighboring communes. Repeat samples were collected from the 83 ZIKV IgM positive participants 1.5 years after the first collection. No new cases of ZIKV infection were detected. In addition, 2 of 3 participants with anti-ZIKV NS1 IgG demonstrated a 4- to 8-fold increase in ZIKV neutralizing antibody titer. Conclusions ZIKV was present in the area around Krong Buk, with the rate of ZIKV-specific antibodies was 1.1% in the community since at least 2016. While the low levels of circulation together with low seroprevalence suggests a limited outbreak in the region, the results also reflect on low levels of protective immunity to Zika within the population. These results provide a better understanding of the current ZIKV epidemic status in the region and demonstrate a need for implementation of more effective ZIKV infection control measures.
Collapse
Affiliation(s)
- Co Thach Nguyen
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.,Department of Virology, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.,Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Nagasaki University, Nagasaki, Japan
| | - Meng Ling Moi
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. .,Department of Virology, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan. .,Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Nagasaki University, Nagasaki, Japan.
| | | | | | - Thi Bich Hau Vu
- National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
| | - Hai Tuan Nguyen
- National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
| | | | - Thi Hien Thu Le
- National Institute of Hygiene and Epidemiology, Hanoi, Vietnam
| | - Le Manh Hung Nguyen
- Tay Nguyen Institute of Hygiene and Epidemiology, Tay Nguyen, Dak Lak, Vietnam
| | - Minh Huong Phu Ly
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.,Department of Virology, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan
| | - Chris Fook Sheng Ng
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
| | - Taichiro Takemura
- Vietnam Research Station, Center for Infectious Disease Research in Asia and Africa, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
| | - Kouichi Morita
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.,Department of Virology, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.,Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Nagasaki University, Nagasaki, Japan
| | - Futoshi Hasebe
- Department of Virology, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.,Vietnam Research Station, Center for Infectious Disease Research in Asia and Africa, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
| |
Collapse
|
22
|
The Endless Challenges of Arboviral Diseases in Brazil. Trop Med Infect Dis 2020; 5:tropicalmed5020075. [PMID: 32397512 PMCID: PMC7345859 DOI: 10.3390/tropicalmed5020075] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 05/07/2020] [Indexed: 12/15/2022] Open
Abstract
In this Editorial, we list and discuss some of the main challenges faced by the population and public health authorities in Brazil concerning arbovirus infections, including the occurrence of concurrent epidemics like the ongoing SARS-CoV-2/COVID-19 pandemic.
Collapse
|
23
|
Lam JH, Smith FL, Baumgarth N. B Cell Activation and Response Regulation During Viral Infections. Viral Immunol 2020; 33:294-306. [PMID: 32326852 DOI: 10.1089/vim.2019.0207] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Acute viral infections are characterized by rapid increases in viral load, leading to cellular damage and the resulting induction of complex innate and adaptive antiviral immune responses that cause local and systemic inflammation. Successful antiviral immunity requires the activation of many immune cells, including T cells, natural killer cells, and macrophages. B cells play a unique part through their production of antibodies that can both neutralize and clear viral particles before virus entry into a cell. Protective antibodies are produced even before the first exposure of a pathogen, through the regulated secretion of so-called natural antibodies that are generated even in the complete absence of prior microbial exposure. An early wave of rapidly secreted antibodies from extrafollicular (EF) responses draws on the preexisting naive or memory repertoire of B cells to induce a strong protective response that in kinetics tightly follows the clearance of acute infections, such as with influenza virus. Finally, the generation of germinal centers (GCs) provides long-term protection through production of long-lived plasma cells and memory B cells, which shape and broaden the B cell repertoire for more effective responses following repeat exposures. In this study, we review B cell responses to acute viral infections, primarily influenza virus, from the earliest nonspecific B-1 cell to early, antigen-specific EF responses and finally to GC responses. Throughout, we address known factors that lead to distinct B cell response outcomes and discuss how their functions effect viral clearance, highlighting the critical contributions of each response type to the induction of highly protective antiviral humoral immunity.
Collapse
Affiliation(s)
- Jonathan H Lam
- Graduate Group in Immunology, Microbiology and Immunology, University of California, Davis, Davis, California, USA.,Center for Comparative Medicine, Microbiology and Immunology, University of California, Davis, Davis, California, USA
| | - Fauna L Smith
- Center for Comparative Medicine, Microbiology and Immunology, University of California, Davis, Davis, California, USA.,Integrated Pathobiology Graduate Group, Microbiology and Immunology, University of California, Davis, Davis, California, USA
| | - Nicole Baumgarth
- Graduate Group in Immunology, Microbiology and Immunology, University of California, Davis, Davis, California, USA.,Center for Comparative Medicine, Microbiology and Immunology, University of California, Davis, Davis, California, USA.,Integrated Pathobiology Graduate Group, Microbiology and Immunology, University of California, Davis, Davis, California, USA.,Department of Pathology, Microbiology and Immunology, University of California, Davis, Davis, California, USA
| |
Collapse
|
24
|
Wang WH, Urbina AN, Wu CC, Lin CY, Thitithanyanont A, Assavalapsakul W, Lu PL, Chen YH, Wang SF. An epidemiological survey of the current status of Zika and the immune interaction between dengue and Zika infection in Southern Taiwan. Int J Infect Dis 2020; 93:151-159. [PMID: 31982624 DOI: 10.1016/j.ijid.2020.01.031] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/13/2020] [Accepted: 01/19/2020] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES This study was performed to examine the current status of Zika and the effects of pre-existing dengue immunity on Zika virus (ZIKV) infection in Southern Taiwan. METHODS A phylogenetic tree was used to analyze the phylogeny of detected ZIKVs. Paired sera from dengue patients were collected for the determination of dengue and Zika infection. Plaque reduction neutralization tests (PRNT) and quantitative reverse transcription PCR (qRT-PCR) were used to determine the titers of neutralizing antibodies and viruses, respectively. An antibody-dependent enhancement (ADE) assay was used to evaluate the effect of anti-dengue antibodies on ZIKV infection. RESULTS Epidemiological data indicated the continuous importation of ZIKV infection from neighboring Zika epidemic countries into Taiwan. A total of 78 dengue patients were enrolled and 21 paired serum samples were obtained. PRNT90 results for the 21 samples identified eight cases of primary dengue infection and 13 cases of secondary dengue infection; two samples were positive for ZIKV (MR766). Results from the ADE assay indicated that convalescent sera from primary and secondary dengue infection patients displayed significant ADE of the ZIKV infection when compared to healthy controls (p < 0.05). CONCLUSIONS This study suggests that pre-existing dengue immunity facilitates ZIKV infection and that the continuous importation of ZIKV infection may pose a threat to indigenous Zika emergence in Southern Taiwan.
Collapse
Affiliation(s)
- Wen-Hung Wang
- Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
| | - Aspiro Nayim Urbina
- Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Program in Tropical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
| | - Chia-Ching Wu
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
| | - Chih-Yen Lin
- Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan
| | - Arunee Thitithanyanont
- Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
| | - Wanchai Assavalapsakul
- Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Po-Liang Lu
- Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan
| | - Yen-Hsu Chen
- Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan
| | - Sheng-Fan Wang
- Center for Tropical Medicine and Infectious Disease, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan; Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
| |
Collapse
|
25
|
Disease Resurgence, Production Capability Issues and Safety Concerns in the Context of an Aging Population: Is There a Need for a New Yellow Fever Vaccine? Vaccines (Basel) 2019; 7:vaccines7040179. [PMID: 31717289 PMCID: PMC6963298 DOI: 10.3390/vaccines7040179] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 10/28/2019] [Accepted: 11/05/2019] [Indexed: 12/19/2022] Open
Abstract
Yellow fever is a potentially fatal, mosquito-borne viral disease that appears to be experiencing a resurgence in endemic areas in Africa and South America and spreading to non-endemic areas despite an effective vaccine. This trend has increased the level of concern about the disease and the potential for importation to areas in Asia with ecological conditions that can sustain yellow fever virus transmission. In this article, we provide a broad overview of yellow fever burden of disease, natural history, treatment, vaccine, prevention and control initiatives, and vaccine and therapeutic agent development efforts.
Collapse
|
26
|
Yellow Fever: Integrating Current Knowledge with Technological Innovations to Identify Strategies for Controlling a Re-Emerging Virus. Viruses 2019; 11:v11100960. [PMID: 31627415 PMCID: PMC6832525 DOI: 10.3390/v11100960] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 09/30/2019] [Accepted: 10/11/2019] [Indexed: 01/17/2023] Open
Abstract
Yellow fever virus (YFV) represents a re-emerging zoonotic pathogen, transmitted by mosquito vectors to humans from primate reservoirs. Sporadic outbreaks of YFV occur in endemic tropical regions, causing a viral hemorrhagic fever (VHF) associated with high mortality rates. Despite a highly effective vaccine, no antiviral treatments currently exist. Therefore, YFV represents a neglected tropical disease and is chronically understudied, with many aspects of YFV biology incompletely defined including host range, host–virus interactions and correlates of host immunity and pathogenicity. In this article, we review the current state of YFV research, focusing on the viral lifecycle, host responses to infection, species tropism and the success and associated limitations of the YFV-17D vaccine. In addition, we highlight the current lack of available treatments and use publicly available sequence and structural data to assess global patterns of YFV sequence diversity and identify potential drug targets. Finally, we discuss how technological advances, including real-time epidemiological monitoring of outbreaks using next-generation sequencing and CRISPR/Cas9 modification of vector species, could be utilized in future battles against this re-emerging pathogen which continues to cause devastating disease.
Collapse
|