%0 Journal Article %T Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection %A Anne S. De Groot %A Leonard Moise %A Andres H. Gutierrez %J Frontiers in Microbiology %D 2014 %I Frontiers Media %R 10.3389/fmicb.2014.00502 %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 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. %K HIV %K HCV %K T-cell epitope %K immunoinformatics %K Vaccines %K cross-reactivity %K regulatory T cells %K Immune Evasion %K JanusMatrix %K T-cell receptor %K MHC class II %K HLA-DR Antigens %U http://www.frontiersin.org/Journal/10.3389/fmicb.2014.00502/abstract