title: Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial.
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.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, USA.
authors.forename: Morgane
authors.initials: M
authors.lastname: Rolland
authors.forename: Sodsai
authors.initials: S
authors.lastname: Tovanabutra
authors.forename: Allan C
authors.initials: AC
authors.lastname: deCamp
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.forename: Eric
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authors.lastname: Sanders-Buell
authors.forename: Laura
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authors.lastname: Heath
authors.forename: Craig A
authors.initials: CA
authors.lastname: Magaret
authors.forename: Meera
authors.initials: M
authors.lastname: Bose
authors.forename: Andrea
authors.initials: A
authors.lastname: Bradfield
authors.forename: Annemarie
authors.initials: A
authors.lastname: O'Sullivan
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Crossler
authors.forename: Teresa
authors.initials: T
authors.lastname: Jones
authors.forename: Marty
authors.initials: M
authors.lastname: Nau
authors.forename: Kim
authors.initials: K
authors.lastname: Wong
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Dana N
authors.initials: DN
authors.lastname: Raugi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Sorensen
authors.forename: Julia N
authors.initials: JN
authors.lastname: Stoddard
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Maust
authors.forename: Wenjie
authors.initials: W
authors.lastname: Deng
authors.forename: John
authors.initials: J
authors.lastname: Hural
authors.forename: Sheri
authors.initials: S
authors.lastname: Dubey
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: John
authors.initials: J
authors.lastname: Shiver
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Fusheng
authors.initials: F
authors.lastname: Li
authors.forename: Steve G
authors.initials: SG
authors.lastname: Self
authors.forename: Jerome
authors.initials: J
authors.lastname: Kim
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Michael N
authors.initials: MN
authors.lastname: Robertson
authors.forename: Ann
authors.initials: A
authors.lastname: Duerr
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Francine E
authors.initials: FE
authors.lastname: McCutchan
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D000939:Epitopes / Q000737:chemistry; D005260:Female; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D010919:Placebos; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D010919:Placebos