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

Autor: Dawood RM; Micrbial Biotechnology Department, National Research Center, 33 Tahrir street, Dokki, Cairo, 12622, Egypt. rmhaemd@hotmail.com., Moustafa RI; Micrbial Biotechnology Department, National Research Center, 33 Tahrir street, Dokki, Cairo, 12622, Egypt.; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL- Centre d'Infection et d'Immunité de Lille, F-59000, Lille, France., Abdelhafez TH; Micrbial Biotechnology Department, National Research Center, 33 Tahrir street, Dokki, Cairo, 12622, Egypt., El-Shenawy R; Micrbial Biotechnology Department, National Research Center, 33 Tahrir street, Dokki, Cairo, 12622, Egypt., El-Abd Y; Micrbial Biotechnology Department, National Research Center, 33 Tahrir street, Dokki, Cairo, 12622, Egypt., Bader El Din NG; Micrbial Biotechnology Department, National Research Center, 33 Tahrir street, Dokki, Cairo, 12622, Egypt., Dubuisson J; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL- Centre d'Infection et d'Immunité de Lille, F-59000, Lille, France., El Awady MK; Micrbial Biotechnology Department, National Research Center, 33 Tahrir street, Dokki, Cairo, 12622, Egypt.
Jazyk: angličtina
Zdroj: BMC infectious diseases [BMC Infect Dis] 2019 Nov 05; Vol. 19 (1), pp. 932. Date of Electronic Publication: 2019 Nov 05.
DOI: 10.1186/s12879-019-4571-5
Abstrakt: 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.
Databáze: MEDLINE
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