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Specificity of CD8(+) T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya

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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349992/
https://www.ncbi.nlm.nih.gov/pubmed/32485938
http://dx.doi.org/10.3390/vaccines8020260
Descripción
Sumario: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.