Institute of Infection and Immunity, St Georges University of London, London UK.
J Gen Virol. 2022 Jan;103(1). doi: 10.1099/jgv.0.001698.
The pandemic caused by SARS-CoV-2 has led to the successful development of effective vaccines however the prospect of variants of SARS-CoV-2 and future coronavirus outbreaks necessitates the investigation of other vaccine strategies capable of broadening vaccine mediated T-cell responses and potentially providing cross-immunity. In this study the SARS-CoV-2 proteome was assessed for clusters of immunogenic epitopes restricted to diverse human leucocyte antigen. These regions were then assessed for their conservation amongst other coronaviruses representative of different alpha and beta coronavirus genera. Sixteen highly conserved peptides containing numerous HLA class I and II restricted epitopes were synthesized from these regions and assessed for their antigenicity against T-cells from individuals with previous SARS-CoV-2 infection. Monocyte derived dendritic cells were generated from these peripheral blood mononuclear cells (PBMC), loaded with SARS-CoV-2 peptides, and used to induce autologous CD4+ and CD8+ T cell activation. The SARS-CoV-2 peptides demonstrated antigenicity against the T-cells from individuals with previous SARS-CoV-2 infection indicating that this approach holds promise as a method to activate anti-SAR-CoV-2 T-cell responses from conserved regions of the virus which are not included in vaccines utilising the Spike protein.
由 SARS-CoV-2 引起的大流行导致了有效疫苗的成功开发，然而，SARS-CoV-2 变体和未来冠状病毒爆发的前景需要研究其他疫苗策略，这些策略能够扩大疫苗介导的 T 细胞反应，并可能提供交叉免疫。在这项研究中，评估了 SARS-CoV-2 蛋白组中受多种人类白细胞抗原限制的免疫原性表位簇。然后评估了这些区域在其他冠状病毒中的保守性，这些冠状病毒代表了不同的α和β冠状病毒属。从这些区域合成了 16 个含有大量 HLA Ⅰ类和Ⅱ类限制表位的高度保守肽，并评估了它们对先前感染过 SARS-CoV-2 的个体 T 细胞的抗原性。从这些外周血单核细胞 (PBMC) 中生成单核细胞衍生的树突状细胞，负载 SARS-CoV-2 肽，并用于诱导同源 CD4+和 CD8+T 细胞激活。SARS-CoV-2 肽对先前感染过 SARS-CoV-2 的个体的 T 细胞具有抗原性，这表明这种方法有希望成为一种从利用 Spike 蛋白的疫苗中不包括的病毒保守区域激活抗 SARS-CoV-2 T 细胞反应的方法。
