NIHR HPRU in Respiratory Infections, Imperial College London, London, England.
National Heart and Lung Institute, Imperial College London, London, England.
Nat Commun. 2022 Jan 10;13(1):80. doi: 10.1038/s41467-021-27674-x.
Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.
已在大流行前的队列中观察到针对 SARS-CoV-2 的交叉反应性免疫应答，并提出其有助于宿主保护。在这里，我们评估了 52 例 COVID-19 家庭接触者，以在 SARS-CoV-2 暴露后最早的时间点捕获免疫反应。使用外周血单核细胞的双细胞因子 FLISpot 测定法，我们对针对刺突、核衣壳、膜、包膜和 ORF1 SARS-CoV-2 表位的 T 细胞进行计数，这些表位与人类地方性冠状病毒发生交叉反应。我们观察到，与转 PCR 阳性的接触者（n=26）相比，尽管接触但仍保持 PCR 阴性的接触者（n=26）中，具有交叉反应性（p=0.0139）和核衣壳特异性（p=0.0355）IL-2 分泌记忆 T 细胞的频率更高；而对刺突的反应频率没有显著差异，这暗示了刺突交叉反应性 T 细胞的保护作用有限。因此，我们的结果与预先存在的非刺突交叉反应性记忆 T 细胞保护 SARS-CoV-2 未感染的接触者免受感染的结果一致，从而支持在第二代疫苗中包含非刺突抗原。
