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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 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??g. Humoral responses to structural epitopes were assayed by ELISA at different times after injection. ELISpot assay was used to evaluate IFN ? 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.

SUBMITTER: Dawood RM

PROVIDER: S-EPMC6833294 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Dawood Reham M RM Moustafa Rehab I RI Abdelhafez Tawfeek H TH El-Shenawy Reem R El-Abd Yasmine Y Bader El Din Noha G NG Dubuisson Jean J El Awady Mostafa K MK

BMC infectious diseases 20191105 1

<h4>Background</h4>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.<h4>Methods</h4>Six peptides derived from conserved epi ...[more]

PMID: 31690267

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Project description:BackgroundDefining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort.MethodsWe compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination.ResultsWe showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination.ConclusionTogether, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity.Trial registrationRegistration is not required for observational studies.FundingThis study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.

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

Publications

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

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