Broad HIV-1 Inhibition in Vitro by Vaccine-Elicited CD8(+) T Cells in African Adults

Publication Type
Journal Article
Year of Publication
2016
Authors
Mutua, G; Farah, B; Langat, R; Indangasi, J; Ogola, S; Onsembe, B; Kopycinski, JT; Hayes, P; Borthwick, NJ; Ashraf, A; Dally, L; Barin, B; Tillander, A; Gilmour, J; De Bont, J; Crook, A; Hannaman, D; Cox, JH; Anzala, O; Fast, PE; Reilly, M; Chinyenze, K; Jaoko, W; Hanke, T; The Hiv-Core 004 Study Group
Secondary
Mol Ther Methods Clin Dev
Volume
3
Pagination
16061
Date Published
08/2016
Keywords
HIV-1; Infectious diseases; T-cell; Translational Research
Abstract

We are developing a pan-clade HIV-1 T-cell vaccine HIVconsv, which could complement Env vaccines for prophylaxis and be a key to HIV cure. Our strategy focuses vaccine-elicited effector T-cells on functionally and structurally conserved regions (not full-length proteins and not only epitopes) of the HIV-1 proteome, which are common to most global variants and which, if mutated, cause a replicative fitness loss. Our first clinical trial in low risk HIV-1-negative adults in Oxford demonstrated the principle that naturally mostly subdominant epitopes, when taken out of the context of full-length proteins/virus and delivered by potent regimens involving combinations of simian adenovirus and poxvirus modified vaccinia virus Ankara, can induce robust CD8(+) T cells of broad specificities and functions capable of inhibiting in vitro HIV-1 replication. Here and for the first time, we tested this strategy in low risk HIV-1-negative adults in Africa. We showed that the vaccines were well tolerated and induced high frequencies of broadly HIVconsv-specific plurifunctional T cells, which inhibited in vitro viruses from four major clades A, B, C, and D. Because sub-Saharan Africa is globally the region most affected by HIV-1/AIDS, trial HIV-CORE 004 represents an important stage in the path toward efficacy evaluation of this highly rational and promising vaccine strategy.