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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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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