Conference Proceeding

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

Dr. Tomas Hanke,
University of Oxford, UK

Professor Tomas Hanke's research aims to develop a universal HIV-1 vaccine, which targets most global virus variants including escape mutants. He strives to maintain a balance between basic and translational research. He oversees a busy pre-clinical programme encompassing HIV-1 epitope discovery and dynamics using mass spectrometry and T-cell assays, studies on immunodominance, depth (number of variants) of epitope recognition and the importance of perfect vaccine-virus epitope matching for effective effector functions. He explores novel vaccine modalities and optimizes their immunogenicity in heterelogous prime-boost regimens in mice and macaques. He co-ordinates a clinical programme assessing candidate HIV vaccines in humans in UK, Europe and Africa.

We are developing a pan-clade HIV-1 T-cell vaccine HIV consv, which could complement Env vaccines for prophylaxis and be key to HIV cure. Our strategy focuses vaccine-elicited effector T-cells on functionally and structurally conserved regions (not full-length proteins and not 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 mostly naturally 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 MVA, 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 HIV consv-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 towards efficacy evaluation of this highly rational and promising vaccine strategy.

Published: 05 May 2017