Broad HIV-1 inhibition in vitro by vaccine-elicited CD8(+) T cells in African adults.
2016
Journal Article
Authors:
Mutua, G.;
Farah, B.;
Langat, R.;
Indangasi, J.;
Ogola, S.;
Onsembe, B.;
Kopycinski, J.T.;
Hayes, P.;
Borthwick, N.J.;
Ashraf, A.;
Dally, L.;
Barin, B.;
Tillander, A.;
Gilmour, J.;
De Bont, J.;
Crook, A.;
Hannaman, D.;
Cox, J.H.;
Anzala, O.;
Fast, P.E.;
Reilly, M.;
Chinyenze, K.;
Jaoko, W.;
Hanke, T.;
Group, T.HivCore 0
Secondary:
Mol Ther Methods Clin Dev
Volume:
3
Pagination:
16061
PMID:
27617268
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.
