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Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial |
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| Authors: | Rolland Morgane Tovanabutra Sodsai deCamp Allan C Frahm Nicole Gilbert Peter B Sanders-Buell Eric Heath Laura Magaret Craig A Bose Meera Bradfield Andrea O'Sullivan Annemarie Crossler Jacqueline Jones Teresa Nau Marty Wong Kim Zhao Hong Raugi Dana N Sorensen Stephanie Stoddard Julia N Maust Brandon S Deng Wenjie Hural John Dubey Sheri Michael Nelson L Shiver John Corey Lawrence Li Fusheng Self Steve G Kim Jerome Buchbinder Susan Casimiro Danilo R Robertson Michael N Duerr Ann McElrath M Juliana McCutchan Francine E Mullins James I |
| Institution: | Department of Microbiology, University of Washington, Seattle, Washington, USA. |
| Abstract: | 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. |
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