A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in mice

Abstract Background Although DAAs hold promise to significantly reduce rates of chronic HCV infections, its eradication still requires development of an effective vaccine. Prolonged T cell responses and cross neutralizing antibodies are ideal for vaccination against the infection. We aimed to design...

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Main Authors: Reham M. Dawood, Rehab I. Moustafa, Tawfeek H. Abdelhafez, Reem El-Shenawy, Yasmine El-Abd, Noha G. Bader El Din, Jean Dubuisson, Mostafa K. El Awady
Format: Article
Language:English
Published: BMC 2019-11-01
Series:BMC Infectious Diseases
Subjects:
HCV
Online Access:http://link.springer.com/article/10.1186/s12879-019-4571-5
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spelling doaj-748e9457195c4bdeb0a07100b62830d42020-11-25T03:59:15ZengBMCBMC Infectious Diseases1471-23342019-11-0119111110.1186/s12879-019-4571-5A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in miceReham M. Dawood0Rehab I. Moustafa1Tawfeek H. Abdelhafez2Reem El-Shenawy3Yasmine El-Abd4Noha G. Bader El Din5Jean Dubuisson6Mostafa K. El Awady7Micrbial Biotechnology Department, National Research CenterMicrbial Biotechnology Department, National Research CenterMicrbial Biotechnology Department, National Research CenterMicrbial Biotechnology Department, National Research CenterMicrbial Biotechnology Department, National Research CenterMicrbial Biotechnology Department, National Research CenterUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL- Centre d’Infection et d’Immunité de LilleMicrbial Biotechnology Department, National Research CenterAbstract Background Although DAAs hold promise to significantly reduce rates of chronic HCV infections, its eradication still requires development of an effective vaccine. Prolonged T cell responses and cross neutralizing antibodies are ideal for vaccination against the infection. We aimed to design and synthesize a 6 multi epitope peptide vaccine candidate and provide evidence for production of extended cellular and neutralizing Abs in mice. Methods Six peptides derived from conserved epitopes in E1, E2 (n = 2),NS4B, NS5A and NS5B were designed, synthesized in a multiple antigenic peptide (MAP) form and administered w/o adjuvant to BALB/c mice as HCVp6-MAP at doses ranging from 800 ng to 16 μg. Humoral responses to structural epitopes were assayed by ELISA at different times after injection. ELISpot assay was used to evaluate IFN ɣ producing CD4+/ CD8+ T- lymphocytes at extended durations i.e. > 20 weeks. Viral neutralization by mice sera was tested for genotypes 2a (JFH1) and a chimeric 2a/4a virus (ED43/JFH1) in HCVcc culture. Results HCVp6-MAP confers potent viral neutralization and specific cellular responses at > 1600 ng/ animal for at least 20 weeks. Conclusion We report on a promising anti HCV vaccine for future studies on permissive hosts and in clinical trials.http://link.springer.com/article/10.1186/s12879-019-4571-5HCVVaccineHumoral responseCellular response
collection DOAJ
language English
format Article
sources DOAJ
author Reham M. Dawood
Rehab I. Moustafa
Tawfeek H. Abdelhafez
Reem El-Shenawy
Yasmine El-Abd
Noha G. Bader El Din
Jean Dubuisson
Mostafa K. El Awady
spellingShingle Reham M. Dawood
Rehab I. Moustafa
Tawfeek H. Abdelhafez
Reem El-Shenawy
Yasmine El-Abd
Noha G. Bader El Din
Jean Dubuisson
Mostafa K. El Awady
A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in mice
BMC Infectious Diseases
HCV
Vaccine
Humoral response
Cellular response
author_facet Reham M. Dawood
Rehab I. Moustafa
Tawfeek H. Abdelhafez
Reem El-Shenawy
Yasmine El-Abd
Noha G. Bader El Din
Jean Dubuisson
Mostafa K. El Awady
author_sort Reham M. Dawood
title A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in mice
title_short A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in mice
title_full A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in mice
title_fullStr A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in mice
title_full_unstemmed A multiepitope peptide vaccine against HCV stimulates neutralizing humoral and persistent cellular responses in mice
title_sort multiepitope peptide vaccine against hcv stimulates neutralizing humoral and persistent cellular responses in mice
publisher BMC
series BMC Infectious Diseases
issn 1471-2334
publishDate 2019-11-01
description Abstract Background Although DAAs hold promise to significantly reduce rates of chronic HCV infections, its eradication still requires development of an effective vaccine. Prolonged T cell responses and cross neutralizing antibodies are ideal for vaccination against the infection. We aimed to design and synthesize a 6 multi epitope peptide vaccine candidate and provide evidence for production of extended cellular and neutralizing Abs in mice. Methods Six peptides derived from conserved epitopes in E1, E2 (n = 2),NS4B, NS5A and NS5B were designed, synthesized in a multiple antigenic peptide (MAP) form and administered w/o adjuvant to BALB/c mice as HCVp6-MAP at doses ranging from 800 ng to 16 μg. Humoral responses to structural epitopes were assayed by ELISA at different times after injection. ELISpot assay was used to evaluate IFN ɣ producing CD4+/ CD8+ T- lymphocytes at extended durations i.e. > 20 weeks. Viral neutralization by mice sera was tested for genotypes 2a (JFH1) and a chimeric 2a/4a virus (ED43/JFH1) in HCVcc culture. Results HCVp6-MAP confers potent viral neutralization and specific cellular responses at > 1600 ng/ animal for at least 20 weeks. Conclusion We report on a promising anti HCV vaccine for future studies on permissive hosts and in clinical trials.
topic HCV
Vaccine
Humoral response
Cellular response
url http://link.springer.com/article/10.1186/s12879-019-4571-5
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