AUTHOR=Moise Leonard , Terry Frances , Gutierrez Andres H. , Tassone Ryan , Losikoff Phyllis , Gregory Stephen H. , Bailey-Kellogg Chris , Martin William D. , De Groot Anne S. TITLE=Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection JOURNAL=Frontiers in Microbiology VOLUME=5 YEAR=2014 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2014.00502 DOI=10.3389/fmicb.2014.00502 ISSN=1664-302X 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.