%A Moise,Leonard
%A Terry,Frances
%A Gutierrez,Andres H.
%A Tassone,Ryan
%A Losikoff,Phyllis
%A Gregory,Stephen H.
%A Bailey-Kellogg,Chris
%A Martin,William D.
%A De Groot,Anne S.
%D 2014
%J Frontiers in Microbiology
%C
%F
%G English
%K HIV,HCV,T-cell epitope,immunoinformatics,Vaccines,cross-reactivity,regulatory T cells,Immune Evasion,JanusMatrix,T-cell receptor,MHC class II,HLA-DR Antigens
%Q
%R 10.3389/fmicb.2014.00502
%W
%L
%M
%P
%7
%8 2014-October-06
%9 Perspective
%+ Dr Anne S. De Groot,EpiVax, Inc.,Providence, RI, USA,dr.annie.degroot@gmail.com
%+ Dr Anne S. De Groot,Institute for Immunology and Informatics, University of Rhode Island,Providence, RI, USA,dr.annie.degroot@gmail.com
%#
%! Improved vaccines thwart viral camouflage
%*
%<
%T Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection
%U https://www.frontiersin.org/articles/10.3389/fmicb.2014.00502
%V 5
%0 JOURNAL ARTICLE
%@ 1664-302X
%X 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.