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

• DOI: 10.1038/nm.2316
• Publication Date: 2011-02-28T07:01:52Z
• Authors: Morgane Rolland; Sodsai Tovanabutra; Allan C deCamp; Nicole Frahm; Peter B Gilbert; Eric Sanders-Buell; Laura Heath; Craig A Magaret; Meera Bose; Andrea Bradfield; Annemarie O'Sullivan; Jacqueline Crossler; Teresa Jones; Marty Nau; Kim Wong; Hong Zhao; Dana N Raugi; Stephanie Sorensen; Julia N Stoddard; Brandon S Maust; Wenjie Deng; John Hural; Sheri Dubey; Nelson L Michael; John Shiver; Lawrence Corey; Fusheng Li; Steve G Self; Jerome Kim; Susan Buchbinder; Danilo R Casimiro; Michael N Robertson; Ann Duerr; M Juliana McElrath; Francine E McCutchan; James I Mullins
• Keywords: AIDS Vaccines; Male; 0301 basic medicine; Molecular Sequence Data; HIV Infections; Article; 3. Good health; Placebos; Epitopes; 03 medical and health sciences; HIV-1; Humans; Female; Phylogeny; T-Lymphocytes, Cytotoxic

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 to the vaccine sequence for sequences from vaccine recipients than from placebo recipients. The most significant signature site distinguishing vaccine from placebo recipients was Gag amino acid 84, a site encompassed by several epitopes contained in the vaccine and restricted by human leukocyte antigen (HLA) alleles common in the study cohort. Moreover, the extended divergence was confined to the vaccine components of the virus (HIV-1 Gag, Pol and Nef) and not found in other HIV-1 proteins. These results represent what is to our knowledge the first evidence of selective pressure from vaccine-induced T cell responses on HIV-1 infection in humans.