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Broad HIV-1 inhibition in vitro by vaccine-elicited CD8(+) T cells in African adults.


Journal Article

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

Mol Ther Methods Clin Dev





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.

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