PMID- 32485938 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240214 IS - 2076-393X (Print) IS - 2076-393X (Electronic) IS - 2076-393X (Linking) VI - 8 IP - 2 DP - 2020 May 29 TI - Specificity of CD8(+) T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya. LID - 10.3390/vaccines8020260 [doi] LID - 260 AB - 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. FAU - Mohamed, Yehia S AU - Mohamed YS AUID- ORCID: 0000-0002-5993-5391 AD - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. AD - Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Cairo 11823, Egypt. FAU - Borthwick, Nicola J AU - Borthwick NJ AD - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. FAU - Moyo, Nathifa AU - Moyo N AD - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. FAU - Murakoshi, Hayato AU - Murakoshi H AD - Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan. FAU - Akahoshi, Tomohiro AU - Akahoshi T AD - Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan. FAU - Siliquini, Francesca AU - Siliquini F AD - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. FAU - Hannoun, Zara AU - Hannoun Z AD - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. FAU - Crook, Alison AU - Crook A AD - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. FAU - Hayes, Peter AU - Hayes P AD - International AIDS Vaccine Initiative IAVI-Human Immunology Laboratory, Imperial College London, London SW10 9NH, UK. FAU - Fast, Patricia E AU - Fast PE AD - International AIDS Vaccine Initiative-New York, New York, NY 10004, USA. FAU - Mutua, Gaudensia AU - Mutua G AD - KAVI-Institute of Clinical Research, University of Nairobi, Nairobi 19676 00202, Kenya. FAU - Jaoko, Walter AU - Jaoko W AD - KAVI-Institute of Clinical Research, University of Nairobi, Nairobi 19676 00202, Kenya. FAU - Silva-Arrieta, Sandra AU - Silva-Arrieta S AD - IrsiCaixa AIDS Research Institute-HIVACAT, Hospital Universitari Germans Trias i Pujol, 08916 Barcelona, Spain. FAU - Llano, Anuska AU - Llano A AD - IrsiCaixa AIDS Research Institute-HIVACAT, Hospital Universitari Germans Trias i Pujol, 08916 Barcelona, Spain. FAU - Brander, Christian AU - Brander C AD - IrsiCaixa AIDS Research Institute-HIVACAT, Hospital Universitari Germans Trias i Pujol, 08916 Barcelona, Spain. AD - Faculty of Medicine, Universitat de Vic-Central de Catalunya (UVic-UCC), 08500 Vic, Spain. AD - Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain. FAU - Takiguchi, Masafumi AU - Takiguchi M AD - Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan. FAU - Hanke, Tomas AU - Hanke T AD - The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. AD - Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan. LA - eng GR - MR/N023668/1/MRC_/Medical Research Council/United Kingdom GR - G1001757/MRC_/Medical Research Council/United Kingdom GR - G1001757 and MR/N023668/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article DEP - 20200529 PL - Switzerland TA - Vaccines (Basel) JT - Vaccines JID - 101629355 PMC - PMC7349992 OTO - NOTNLM OT - African HLA OT - CD8 epitopes OT - HIV vaccine OT - HIVconsv OT - HLA class I epitopes OT - T cell vaccine OT - conserved regions COIS- The authors declare no conflict of interest with the subject matter other than T Hanke is a coinventor on patents WO06123156, WO98/056919, PCT/US2014/058422, and EP14846993.5. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2020/06/04 06:00 MHDA- 2020/06/04 06:01 PMCR- 2020/05/29 CRDT- 2020/06/04 06:00 PHST- 2020/05/04 00:00 [received] PHST- 2020/05/20 00:00 [revised] PHST- 2020/05/25 00:00 [accepted] PHST- 2020/06/04 06:00 [entrez] PHST- 2020/06/04 06:00 [pubmed] PHST- 2020/06/04 06:01 [medline] PHST- 2020/05/29 00:00 [pmc-release] AID - vaccines8020260 [pii] AID - vaccines-08-00260 [pii] AID - 10.3390/vaccines8020260 [doi] PST - epublish SO - Vaccines (Basel). 2020 May 29;8(2):260. doi: 10.3390/vaccines8020260.