Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya
Mohamed, Yehia S.
Borthwick, Nicola J.
Fast, Patricia E.
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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. View Full-Text
CitationMohamed, Y.S.; Borthwick, N.J.; Moyo, N.; Murakoshi, H.; Akahoshi, T.; Siliquini, F.; Hannoun, Z.; Crook, A.; Hayes, P.; Fast, P.E.; Mutua, G.; Jaoko, W.; Silva-Arrieta, S.; Llano, A.; Brander, C.; Takiguchi, M.; Hanke, T. Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya. Vaccines 2020, 8, 260.
University of Nairobi
SubjectHIV vaccine; HIVconsv; conserved regions; CD8 epitopes; HLA class I epitopes; T cell vaccine; African HLA
RightsAttribution-NonCommercial-NoDerivs 3.0 United States
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