Vaccines (May 2020)

Specificity of CD8<sup>+</sup> T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya

  • Yehia S. Mohamed,
  • Nicola J. Borthwick,
  • Nathifa Moyo,
  • Hayato Murakoshi,
  • Tomohiro Akahoshi,
  • Francesca Siliquini,
  • Zara Hannoun,
  • Alison Crook,
  • Peter Hayes,
  • Patricia E. Fast,
  • Gaudensia Mutua,
  • Walter Jaoko,
  • Sandra Silva-Arrieta,
  • Anuska Llano,
  • Christian Brander,
  • Masafumi Takiguchi,
  • Tomáš Hanke

DOI
https://doi.org/10.3390/vaccines8020260
Journal volume & issue
Vol. 8, no. 2
p. 260

Abstract

Read online

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.

Keywords