Broad HIV-1 inhibition in vitro by vaccine-elicited cd8(+) t cells in African adults.
Date
2016Author
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
Cox, JH
Anzala, O
Fast, PE
Reilly, M
Chinyenze, K
Jaoko, W
Hanke, T
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
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.
Citation
Mol Ther Methods Clin Dev. 2016 Aug 31;3:16061. doi: 10.1038/mtm.2016.61. eCollection 2016.Publisher
University of Nairobi
Rights
Attribution-NonCommercial-NoDerivs 3.0 United StatesUsage Rights
http://creativecommons.org/licenses/by-nc-nd/3.0/us/Collections
- Faculty of Health Sciences (FHS) [10387]
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