title: Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection.
abstract: Despite years of research, vaccines against HIV and HCV are not yet available, due largely to effective viral immunoevasive mechanisms. A novel escape mechanism observed in viruses that cause chronic infection is suppression of viral-specific effector CD4(+) and CD8(+) T cells by stimulating regulatory T cells (Tregs) educated on host sequences during tolerance induction. Viral class II MHC epitopes that share a T cell receptor (TCR)-face with host epitopes may activate Tregs capable of suppressing protective responses. We designed an immunoinformatic algorithm, JanusMatrix, to identify such epitopes and discovered that among human-host viruses, chronic viruses appear more human-like than viruses that cause acute infection. Furthermore, an HCV epitope that activates Tregs in chronically infected patients, but not clearers, shares a TCR-face with numerous human sequences. To boost weak CD4(+) T cell responses associated with persistent infection, vaccines for HIV and HCV must circumvent potential Treg activation that can handicap efficacy. Epitope-driven approaches to vaccine design that involve careful consideration of the T cell subsets primed during immunization will advance HIV and HCV vaccine development.
authors.affiliation: EpiVax, Inc. , Providence, RI, USA ; Institute for Immunology and Informatics, University of Rhode Island , Providence, RI, USA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Moise
authors.affiliation: EpiVax, Inc. , Providence, RI, USA.
authors.forename: Frances
authors.initials: F
authors.lastname: Terry
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island , Providence, RI, USA.
authors.forename: Andres H
authors.initials: AH
authors.lastname: Gutierrez
authors.affiliation: Institute for Immunology and Informatics, University of Rhode Island , Providence, RI, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Tassone
authors.affiliation: Department of Medicine, Rhode Island Hospital and the Warren Alpert Medical School at Brown University , Providence, RI, USA.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Losikoff
authors.affiliation: EpiVax, Inc. , Providence, RI, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gregory
authors.affiliation: Department of Computer Science, Dartmouth College , Hanover, NH, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Bailey-Kellogg
authors.affiliation: EpiVax, Inc. , Providence, RI, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Martin
authors.affiliation: EpiVax, Inc. , Providence, RI, USA ; Institute for Immunology and Informatics, University of Rhode Island , Providence, RI, USA.
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
keywords: HCV; HIV; MHC class II; T cell epitope; cross-reactivity; immunoinformatics; regulatory T cells; vaccines