Broad HIV-1 inhibition in vitro by vaccine-elicited CD8(+) T cells in African adults.
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., Hiv-Core 004 Study Group T.
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.