Immunization with a subunit hepatitis C virus vaccine elicits pan-genotypic neutralizing antibodies and intra-hepatic T-cell responses in non-human primates

Abstract:

Background:

The global control of hepatitis C virus (HCV) infection remains a great burden, due to the high prices and potential drug resistance of the new direct-acting antivirals (DAAs) as well as the risk of reinfection in DAA-cured patients. Thus, a prophylactic vaccine for HCV is of great importance. We previously reported a single recombinant soluble E2 (sE2) vaccine produced in insect cells was able to induce broadly neutralizing antibodies (NAbs) and prevent HCV infection in mice. Here the sE2 vaccine was evaluated in non-human primates.

Methods:

Rhesus macaques were immunized with sE2 vaccine in combination with different adjuvants. Vaccine-induced NAbs in antisera were tested for neutralization activities against a panel of cell culture-derived HCV (HCVcc), while T-cell responses were evaluated in splenocytes, PBMC and hepatic lymphocytes.

Results:

sE2 is able to elicit NAbs against HCVcc harboring structural proteins from multiple HCV genotypes in rhesus macaques. Moreover, sE2-immunized macaques developed systemic and intra-hepatic memory T cells specific for E2. A significant correlation between the sE2-specific IgG titers and neutralization spectrum was observed, highlighting the essential role of sE2 immunogenicity on achieving broad NAbs.

Conclusions:

sE2 is a promising HCV vaccine candidate that warrants further pre-clinical and clinical development.

Publisher's Version

Last updated on 08/14/2017