Abstract
BackgroundAlthough 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.MethodsSix 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.ResultsHCVp6-MAP confers potent viral neutralization and specific cellular responses at > 1600 ng/ animal for at least 20 weeks.ConclusionWe report on a promising anti HCV vaccine for future studies on permissive hosts and in clinical trials.
Highlights
direct-acting antivirals (DAAs) hold promise to significantly reduce rates of chronic Hepatitis C Virus (HCV) infections, its eradication still requires development of an effective vaccine
Whereas the 3 peptides derived from the nonstructural proteins (NS4B, NS5A, NS5B) have been shown to trigger HCV-specific CD4+ T cell response in subjects who spontaneously cleared the infection [13]
Plates were coated with either individual envelope peptides linked to keyhole limpet hemocyanin (KLH) protein i.e.KLH-315, KLH-412 and KLH-517, a mixture of the 3 KLH-linked peptides (KLH-mix) or a mixture of 3 multiple antigenic peptide (MAP) peptides (MAP-mix)
Summary
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. 71 million patients are chronically infected worldwide [3]. Egypt had the highest global HCV epidemic witj 14% prevalence of chronic infection [4]. It was reported that the gpE1 region is more conserved and less immunogenic than gpE2, minimizing chances to generate neutralizing antibodies to gpE1 epitopes. GpE2 interacts with HCV receptor CD81 and is the major target of neutralizing antibodies. GpE2 has a hypervariable region, called HVR1, at its N-terminus which contains a highly variable non-conformational neutralizing epitope [8, 9].
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