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

Background: One of the major obstacles in the design of an effective vaccine against HIV- 1 is the hypervariability of the HIV- 1 envelope glycoprotein. Most HIV- 1 vaccine candidates have utilized envelope glycoprotein from a single virus isolate, but to date, none of them elicited broadly reactive humoral immunity. Herein, we hypothesised that a cocktail of HIV- 1 gp120 proteins containing multiple epitopes may increase the breadth of immune responses against HIV- 1. We compared and evaluated the immunogenicity of HIV- 1 vaccines containing either gp120 protein alone or in combinations of four or fourteen gp120s from different primary HIV- 1 isolates in immunized hamsters. Results: 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/ E. Conclusion: Although 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.