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- Title
Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya.
- Authors
Mohamed, Yehia S.; Borthwick, Nicola J.; Moyo, Nathifa; Murakoshi, Hayato; Akahoshi, Tomohiro; Siliquini, Francesca; Hannoun, Zara; Crook, Alison; Hayes, Peter; Fast, Patricia E.; Mutua, Gaudensia; Jaoko, Walter; Silva-Arrieta, Sandra; Llano, Anuska; Brander, Christian; Takiguchi, Masafumi; Hanke, Tomáš
- Abstract
Sub-Saharan Africa carries the biggest burden of the human immunodeficiency virus type 1 (HIV-1)/AIDS epidemic and is in an urgent need of an effective vaccine. CD8+ T cells are an important component of the host immune response to HIV-1 and may need to be harnessed if a vaccine is to be effective. CD8+ T cells recognize human leukocyte antigen (HLA)-associated viral epitopes and the HLA alleles vary significantly among different ethnic groups. It follows that definition of HIV-1-derived peptides recognized by CD8+ T cells in the geographically relevant regions will critically guide vaccine development. Here, we study fine details of CD8+ T-cell responses elicited in HIV-1/2-uninfected individuals in Nairobi, Kenya, who received a candidate vaccine delivering conserved regions of HIV-1 proteins called HIVconsv. Using 10-day cell lines established by in vitro peptide restimulation of cryopreserved PBMC and stably HLA-transfected 721.221/C1R cell lines, we confirm experimentally many already defined epitopes, for a number of epitopes we define the restricting HLA molecule(s) and describe four novel HLA-epitope pairs. We also identify specific dominance patterns, a promiscuous T-cell epitope and a rescue of suboptimal T-cell epitope induction in vivo by its functional variant, which all together inform vaccine design.
- Subjects
NAIROBI (Kenya); SUB-Saharan Africa; HLA histocompatibility antigens; VACCINE development; T cells; HISTOCOMPATIBILITY antigens; EPITOPES; VACCINATION
- Publication
Vaccines, 2020, Vol 8, Issue 2, p260
- ISSN
2076-393X
- Publication type
Article
- DOI
10.3390/vaccines8020260