Smarter Vaccine Design Will Circumvent Regulatory T Cell-Mediated Evasion in Chronic HIV and HCV Infection
Date of Original Version
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 L, Terry F, Gutierrez AH, Tassone R, Losikoff P, Gregory SH, Bailey-Kellogg C, Martin WD, De Groot AS. (2014). "Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection." Front. Microbiol. 5:502.
Available at: http://dx.doi.org/10.3389/fmicb.2014.00502
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
All rights reserved under copyright.
This Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.