Genetic impact of vaccination on breakthrough HIV-1 sequences from the Step trial

We analyzed HIV-1 genome sequences from 68 newly-infected volunteers in the Step HIV-1 vaccine trial. To determine whether the vaccine exerted selective T-cell pressure on breakthrough viruses, we identified potential T-cell epitopes in the founder sequences and compared them to epitopes in the vaccine. We found greater distances for sequences from vaccine recipients than from placebo recipients (p-values ranging from < 0.0001 to 0.09). The most significant signature site distinguishing vaccine from placebo recipients was Gag-84, a site encompassed by several epitopes contained in the vaccine and restricted by HLA alleles common in the cohort. Moreover, the extended divergence was confined to the vaccine components of the virus (Gag, Pol, Nef) and not found in other HIV-1 proteins. These results represent the first evidence of selective pressure from vaccine-induced T-cell responses on HIV-1 infection.