Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters

We amplified and characterized 14 different gp120s from primary subtype B isolates with both syncytium and non-syncytium inducing properties, and expressed the proteins in Chinese Hamster Ovary (CHO) cell lines. Purified proteins were used either alone or in combinations of four or fourteen different gp120s to vaccinate golden hamsters. The polyvalent vaccine showed higher antibody titers to HIV-1 subtype B isolates MN and SF162 compared to the groups that received one or four gp120 proteins. However, the polyvalent vaccine was not able to show higher neutralizing antibody responses against HIV-1 primary isolates. Interestingly, the polyvalent vaccine group had the highest proliferative immune responses and showed a substantial proportion of cross-subtype CD4 reactivity to HIV-1 subtypes B, C, and A/EAlthough the polyvalent approach achieved only a modest increase in the breadth of humoral and cellular immunity, the qualitative change in the vaccine (14 vs. 1 gp120) resulted in a quantitative improvement in vaccine-induced immunity.HIV-1 gp120 is a major target for neutralizing antibodies (Nabs) and for this reason it is an important HIV immunogen to include in vaccine formulations [1-3]. However, the diversity of gp120 has proven to be a significant challenge to HIV-1 vaccine development. The structure of gp120 contains variable loops (V1-V5) which likely hide critical conserved epitope sites favoured by the Nabs. Furthermore, the crystallography structure of gp120 indicates that the protein is covered by carbohydrates which facilitates viral escape from Nabs [4,5]. Genetic variability in HIV-gp120 between groups M, N and O also affect the induction of Nabs [6,7]. These factors complicate the design of an effective candidate vaccine against HIV.Previous vaccine studies focus on single HIV immunogens and although some of these studies show an increase in CD4/CD8+T cell immune responses, the immunogens used were not able to induce potent Nabs that mediate sterilizing