Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection.
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.
['Moise|Leonard|L|', 'Terry|Frances|F|', 'Gutierrez|Andres H|AH|', 'Tassone|Ryan|R|', 'Losikoff|Phyllis|P|', 'Gregory|Stephen H|SH|', 'Bailey-Kellogg|Chris|C|', 'Martin|William D|WD|', 'De Groot|Anne S|AS|']
vaccines HIV HCV regulatory T cells immunoinformatics MHC class II T cell epitope cross-reactivity