Humoral and cellular immune responses in RNA viral infections: Immunogenicity of HIV-1, HCV and SARS-CoV candidate vaccines in animal models

Abstract

It is difficult to induce protective immunity against most RNA viruses. However, there is strong evidence that humoral and especially cellular immune responses play crucial roles in the control of established RNA viral infections. Thus, an ideal vaccine should be able to induce strong specific antibody titer as well as a robust T-helper and T-cell cytotoxic response. Here, correlates of protective immunity against HIV-1, HCV and SARS-CoV were assessed. Monocistronic and polycistronic DNA constructs containing structural HIV-l, and SARS genes were designed. The structural proteins (HIV- gpl20, gag, pol, HCV-core, E1/E2 and SARS-NC) were also expressed, purified and characterized in mammalian and bacterial cell lines. HLA-A2.1 and B6 mice were immunized with different combinations of DNA constructs, recombinant proteins and novel adjuvants. Humoral responses were measured by titrating of specific antibodies and cell-mediated immune responses were identified by Th1/Th2 cytokine expression, lymphocyte proliferation, intracellular cytokine staining, HLA-peptide dimer assay, and ELISPOT. The first study in HIV-1 showed that a combination of DNA single constructs, protein and adjuvant induce a higher immune response compared to the DNA or/and protein alone. In the second HIV-1 approach, a synergistic effect between HIV/HCV antigens was detected that may lead to induction of multi-specific immune responses against both HIV and HCV. In the third study (SARS project), a high level of specific SARS-CD8+ T-cell response was demonstrated in mice that received DNA encoding the SARS-nucleocapsid, protein and XIAP (X-link inhibitor of apoptosis) as an adjuvant.