美国拉荷亚免疫学研究所Alba Grifoni小组在研究中取得进展。他们开发出高度保守的冠状病毒序列被人类T细胞广泛识别。该项研究成果发表在2025年8月6日出版的《细胞》上。
在这项研究中，该课题组人员将综合表位定位与序列保守分析相结合，以鉴定保守的T细胞表位区域（CTERs），其占完整SARS-CoV-2蛋白质组的12%。研究团队发现SARS-CoV-2 CTER特异性T细胞交叉反应性地识别来自多个β冠状病毒亚属的序列。重要的是，与仅靶向刺突蛋白的T细胞相比，结合非刺突蛋白的CTERs显著增强了T细胞的交叉反应电位和人类白细胞抗原（HLA）覆盖率。他们的发现为多抗原疫苗策略奠定了基础，该策略包括非刺突蛋白，以在更广泛的β冠状病毒主题范围内扩展交叉反应免疫。
研究人员表示，COVID-19大流行突出表明，迫切需要能够应对新出现的病毒威胁的疫苗战略。乙型冠状病毒主题，包括严重急性呼吸综合征冠状病毒（SARS-CoV）、中东呼吸综合征（MERS）和SARS-CoV-2，由于其人畜共患的潜力和遗传多样性，存在重大的大流行风险。T细胞介导的免疫表现出持久的应答和强烈的交叉反应性，为在病毒家族中实现广泛免疫提供了一条有希望的途径。
附：英文原文
Title: Highly conserved Betacoronavirus sequences are broadly recognized by human T cells
Author: Tertuliano Alves Pereira Neto, Christian Zmasek, Liliana Avalos, John Sidney, Raphael Trevizani, Elizabeth Phillips, Simon Mallal, April Frazier, Gene S. Tan, Richard H. Scheuermann, Alessandro Sette, Alba Grifoni
Issue&Volume: 2025-08-06
Abstract: The COVID-19 pandemic highlighted the critical need for vaccine strategies capable of addressing emerging viral threats. Betacoronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS), and SARS-CoV-2, present significant pandemic risks due to their zoonotic potential and genetic diversity. T cell-mediated immunity has demonstrated durable responses and strong cross-reactivity, offering a promising avenue for achieving broad immunity within a viral family. In this study, we combined comprehensive epitope mapping with sequence conservation analyses to identify conserved T cell epitope regions (CTERs), which constitute 12% of the complete SARS-CoV-2 proteome. We showed that SARS-CoV-2 CTER-specific T cells cross-reactively recognize sequences from multiple Betacoronavirus subgenera. Importantly, incorporating CTERs from non-spike proteins significantly enhanced T cell cross-reactivity potential and human leukocyte antigen (HLA) coverage compared with T cells targeting only spike proteins. Our findings lay the groundwork for a multi-antigen vaccine strategy that includes non-spike proteins to expand cross-reactive immunity across a broader spectrum of Betacoronaviruses.
DOI: 10.1016/j.cell.2025.07.015
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00804-9