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

• Main Authors: Gaudensia Mutua, Bashir Farah, Robert Langat, Jackton Indangasi, Simon Ogola, Brian Onsembe, Jakub T Kopycinski, Peter Hayes, Nicola J Borthwick, Ambreen Ashraf, Len Dally, Burc Barin, Annika Tillander, Jill Gilmour, Jan De Bont, Alison Crook, Drew Hannaman, Josephine H Cox, Omu Anzala, Patricia E Fast, Marie Reilly, Kundai Chinyenze, Walter Jaoko, Tomáš Hanke
• Format: Article
• Language: English
• Published: Elsevier 2016-01-01
• Series: Molecular Therapy: Methods & Clinical Development
• Online Access: http://www.sciencedirect.com/science/article/pii/S2329050117300311

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.