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
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Cairo 11823, Egypt.
Vaccines (Basel). 2020 May 29;8(2):260. doi: 10.3390/vaccines8020260.
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.
撒哈拉以南非洲地区承受着人类免疫缺陷病毒1型(HIV-1)/艾滋病疫情的最大负担,迫切需要一种有效的疫苗。CD8 T细胞是宿主对HIV-1免疫反应的重要组成部分,如果疫苗要发挥作用,可能需要利用这些细胞。CD8 T细胞识别与人类白细胞抗原(HLA)相关的病毒表位,而HLA等位基因在不同种族群体中差异很大。因此,确定在地理相关区域中被CD8 T细胞识别的HIV-1衍生肽对于指导疫苗开发至关重要。在此,我们研究了肯尼亚内罗毕未感染HIV-1/2的个体接种一种名为HIVconsv的递送HIV-1蛋白保守区域的候选疫苗后引发的CD8 T细胞反应的详细情况。我们使用通过对冷冻保存的外周血单核细胞(PBMC)进行体外肽再刺激建立的10天细胞系以及稳定转染HLA的721.221/C1R细胞系,通过实验证实了许多已确定的表位,确定了一些表位的限制性HLA分子,并描述了四对新的HLA-表位对。我们还确定了特定的优势模式、一个混杂的T细胞表位以及其功能变体在体内对次优T细胞表位诱导的挽救作用,这些都为疫苗设计提供了依据。