Analysis of HLAA*02 association with vaccine efficacy in the RV144 HIV-1 vaccine trial.

Publication Type:

Journal Article

Source:

Journal of virology (2014)

Keywords:

2014, Clinical Research Division, June 2014, Vaccine and Infectious Disease Division

Abstract:

The RV144 HIV-1 vaccine trial demonstrated partial efficacy of 31% against HIV-1 infection. Studies into possible correlates of protection found that antibodies specific to the V1/V2 region of envelope correlated inversely with infection risk and that viruses isolated from trial participants contained genetic signatures of vaccine-induced pressure in the V1/V2 region. We explored the hypothesis that the genetic signatures in V1/V2 could be partly attributed to selection by vaccine primed T cells. We performed a T-cell based sieve analysis of breakthrough viruses in the RV144 trial and found evidence of predicted HLA binding escape that was greater in vaccine versus placebo recipients. The predicted escape depended on class I HLA A*02 and A*11 restricted epitopes in the MN-strain rgp120 vaccine immunogen. Though we hypothesized that this was indicative of post-acquisition selection pressure, we also found that vaccine efficacy (VE) was greater in A*02(+) compared to A*02(-) participants (VE=54% vs. 3%, p=0.05). Vaccine efficacy against viruses with a lysine residue at site 169, important to antibody binding and implicated in vaccine-induced immune pressure, was also greater in A*02(+) participants (VE=74% vs. 15%, p=0.02). Additionally, a reanalysis of vaccine-induced immune responses focused on those that were shown to correlate with infection risk, suggested that the humoral response may have differed in A*02(+) participants. These exploratory and hypothesis-generating analyses indicate there may be an association between a class I HLA allele and vaccine efficacy, highlighting the importance of considering HLA alleles and host immune genetics in HIV vaccine trials.