Novel knowledge about the influence of hepatitis C virus structural proteins ratio in vaccine preparations to induce a protective immune response in a challenge model with a surrogate virus
Abstract
The incomplete definition of immunologic parameters that correlates with the protection against HCV infection has limited the development of a vaccine against this pathogen. Several studies advocate for the induction of strong cellular immune response against viral antigens, as well as neutralizing antibodies against HCV E2 envelope protein, as a success criteria. However, the influence of several antigens against each others in a protein preparation and the impact on the immunogenicity, have not been explored yet. In the present study a factorial design was used to generate several HCV vaccine preparations with the structural core, E1 and E2 proteins as antigens. An optimal antigen composition was chosen based on the lymphoproliferative response against HCV as well as protection against challenge with a surrogate virus in BALBC/c mice. The protein ratio (1:160:160), with 0.1 µg of Co.120-16.7 µg of E1.340-16.7 µg E2.680 (Co-E1-E2) was selected as the optimal composition to induce a functional immune response in mice. Additionally, strong humoral immune response against the 412-438 amino acid region from HCV E2 protein was detected when African green monkeys were immunized with Co-E1-E2. This region includes a conserved epitope, involved in T cell lymphoproliferative response against Co.120 and E2.680 proteins as well as in HCV neutralization. The results evidenced the relevance of proportion between HCV structural antigens in vaccine preparations for eliciting successful immune response.
