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Broad HIV-1 inhibition in vitro by vaccine-elicited CD8(+) T cells in African adults.
- Source :
-
Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2016 Aug 31; Vol. 3, pp. 16061. Date of Electronic Publication: 2016 Aug 31 (Print Publication: 2016). - Publication Year :
- 2016
-
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.
Details
- Language :
- English
- ISSN :
- 2329-0501
- Volume :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular therapy. Methods & clinical development
- Publication Type :
- Academic Journal
- Accession number :
- 27617268
- Full Text :
- https://doi.org/10.1038/mtm.2016.61