Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts.
Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts.
复制标题
DOI：
10.1038/s41467-021-27674-x
复制
发表时间：
2022-01-10
影响因子：
16.6
通讯作者：
Lalvani A
中科院分区：
文献类型：
--
作者：
Kundu R;Narean JS;Wang L;Fenn J;Pillay T;Fernandez ND;Conibear E;Koycheva A;Davies M;Tolosa-Wright M;Hakki S;Varro R;McDermott E;Hammett S;Cutajar J;Thwaites RS;Parker E;Rosadas C;McClure M;Tedder R;Taylor GP;Dunning J;Lalvani A
对SARS-CoV-2的交叉反应性免疫应答已在大流行前的队列中观察到，并被认为有助于宿主保护。在这里，我们评估了52个COVID-19家庭接触者，以在SARS-CoV-2暴露后的最早时间点捕获免疫反应。使用外周血单核细胞的双重细胞因子FLISpot试验，我们计数了与人类地方性冠状病毒交叉反应的刺突、核衣壳、膜、包膜和ORF 1 SARS-CoV-2表位特异性T细胞的频率。我们观察到更高频率的交叉反应（p = 0.0139），核衣壳蛋白特异性（p = 0.0355）与转化为PCR阳性的接触者（n = 26）相比，尽管暴露但仍保持PCR阴性的接触者（n = 26）中分泌IL-2的记忆T细胞;没有观察到对刺突的应答频率的显著差异，提示刺突交叉反应性T细胞的保护功能有限。因此，我们的结果与预先存在的非刺突交叉反应记忆T细胞保护SARS-CoV-2-naïve接触者免受感染一致，从而支持在第二代疫苗中包含非刺突抗原。虽然人冠状病毒和SARS-CoV-2之间的交叉反应免疫可能有助于宿主保护，但验证证据仍然很少。在这里，作者评估了52名与SARS-CoV-2有早期接触的供体队列，以将交叉反应性T细胞的较高频率与较低的感染率相关联。
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. While cross-reactive immunity between human coronavirus and SARS-CoV-2 may contribute to host protection, validating evidences are still scarce. Here the authors assess a cohort of 52 donors with immediate-early contact with SARS-CoV-2 to correlate higher frequency of cross-reactive T cells with lower infection rate.
登录
查看更多内容
影响因子：
32.4
作者：
Ferretti AP;Kula T;Wang Y;Nguyen DMV;Weinheimer A;Dunlap GS;Xu Q;Nabilsi N;Perullo CR;Cristofaro AW;Whitton HJ;Virbasius A;Olivier KJ Jr;Buckner LR;Alistar AT;Whitman ED;Bertino SA;Chattopadhyay S;MacBeath G
通讯作者：
MacBeath G
影响因子：
64.8
作者：
Sallusto, F;Lenig, D;Lanzavecchia, A
通讯作者：
Lanzavecchia, A
影响因子：
6.7
作者：
Eguia RT;Crawford KHD;Stevens-Ayers T;Kelnhofer-Millevolte L;Greninger AL;Englund JA;Boeckh MJ;Bloom JD
通讯作者：
Bloom JD
影响因子：
7.8
作者：
Rammensee HG;Gouttefangeas C;Heidu S;Klein R;Preuß B;Walz JS;Nelde A;Haen SP;Reth M;Yang J;Tabatabai G;Bösmüller H;Hoffmann H;Schindler M;Planz O;Wiesmüller KH;Löffler MW
通讯作者：
Löffler MW
DOI：
10.1126/science.aba9301
发表时间：
2020-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Habibi MS;Thwaites RS;Chang M;Jozwik A;Paras A;Kirsebom F;Varese A;Owen A;Cuthbertson L;James P;Tunstall T;Nickle D;Hansel TT;Moffatt MF;Johansson C;Chiu C;Openshaw PJM
通讯作者：
Openshaw PJM