%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.