Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model

BACKGROUND: Current data suggest that an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine should elicit both adaptive humoral and cell mediated immune responses. Such a vaccine will also need to protect against infection from a range of heterologous viral variants. Here we have developed a simian-human immunodeficiency virus (SHIV) based model in cynomolgus macaques to investigate the breadth of protection conferred by HIV-1(W61D) recombinant gp120 vaccination against SHIV(sbg) and SHIV(SF33) challenge, and to identify correlates of protection. RESULTS: High titres of anti-envelope antibodies were detected in all vaccinees. The antibodies reacted with both the homologous HIV-1(W61D) and heterologous HIV-1(IIIB) envelope rgp120 which has an identical sequence to the SHIV(sbg) challenge virus. Significant titres of virus neutralising antibodies were detected against SHIV(W61D) expressing an envelope homologous with the vaccine, but only limited cross neutralisation against SHIV(sbg), SHIV-4 and SHIV(SF33) was observed. Protection against SHIV(sbg) infection was observed in vaccinated animals but none was observed against SHIV(SF33) challenge. Transfer of immune sera from vaccinated macaques to naive recipients did not confer protection against SHIV(sbg) challenge. In a follow-up study, T cell proliferative responses detected after immunisation with the same vaccine against a single peptide present in the second conserved region 2 of HIV-1 (W61D) and HIV-1 IIIB gp120, but not SF33 gp120. CONCLUSIONS: Following extended vaccination with a HIV-1 rgp120 vaccine, protection was observed against heterologous virus challenge with SHIV(sbg), but not SHIV(SF33). Protection did not correlate with serological responses generated by vaccination, but might be associated with T cell proliferative responses against an epitope in the second constant region of HIV-1 gp120. Broader protection may be obtained with recombinant HIV-1 envelope based vaccines formulated with adjuvants that generate proliferative T cell responses in addition to broadly neutralising antibodies.