Assessment of T-cell Reactivity to the SARS-CoV-2 Omicron Variant by Immunized Individuals.
Assessment of T-cell Reactivity to the SARS-CoV-2 Omicron Variant by Immunized Individuals.
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DOI：
10.1001/jamanetworkopen.2022.10871
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发表时间：
2022-04-01
影响因子：
13.8
通讯作者：
Borsellino, Giovanna
中科院分区：
文献类型：
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作者：
De Marco, Lorenzo;D'Orso, Silvia;Pirronello, Marta;Verdiani, Alice;Termine, Andrea;Fabrizio, Carlo;Capone, Alessia;Sabatini, Andrea;Guerrera, Gisella;Placido, Roberta;Sambucci, Manolo;Angelini, Daniela F.;Giannessi, Flavia;Picozza, Mario;Caltagirone, Carlo;Salvia, Antonino;Volpe, Elisabetta;Balice, Maria Pia;Rossini, Angelo;Rotzschke, Olaf;Giardina, Emiliano;Battistini, Luca;Borsellino, Giovanna
在免疫个体中，与SARS-CoV-2的Omicron变体相关的细胞免疫是什么？在这项队列研究中，在61名接种了COVID-19疫苗的个体中，80%的参与者检测到对Omicron刺突蛋白突变区域的细胞反应。与疫苗株相比，突变与t细胞识别显著降低有关，而100%的参与者对整个刺突蛋白具有反应性，对SARS-CoV-2的剩余免疫力比例估计为87%。这些发现表明，尽管其刺突蛋白发生突变，但对Omicron变体的细胞免疫仍保持不变；因此，免疫接种可以保护人们免受欧米克隆变异的严重COVID-19。本队列研究评估了接种过SARS-CoV-2疫苗的个体中t细胞对SARS-CoV-2 Omicron变体的反应性。高传染性SARS-CoV-2的Omicron变体的出现，以及先前感染过SARS-CoV-2或接种过SARS-CoV-2的个体的血清中和效力显著降低的发现，突出了研究细胞免疫以估计对新SARS-CoV-2变体的免疫保护程度的重要性。确定对SARS-CoV-2具有（天然和/或疫苗诱导）免疫力的个体对组粒变异的t细胞反应性。这是一项队列研究，于2021年12月20日至21日在意大利罗马的圣卢西亚基金会研究所进行，其中包括卫生保健工作者和科学家志愿者。从新鲜抽取的血液样本中分离淋巴细胞，并立即检测其对SARS-CoV-2刺突蛋白的反应性。主要结果是测定t细胞对Omicron BA.1 SARS-CoV-2变异刺突蛋白突变区域的反应性，并通过肽库刺激评估剩余t细胞对刺突蛋白的免疫。共61名志愿者(平均（范围）年龄41.62岁（21-62岁）；38名女性（62%）具有不同的疫苗接种和SARS-CoV-2感染背景。CD4+ T细胞对覆盖Omicron突变区域的多肽反应的中位数（范围）频率为0.039%(0%-2.356%)，与祖先菌株相同区域特异性CD4+细胞的频率（0.109%[0%-2.376%]）相比下降了64%。在CD8+ T细胞中，中位数（范围）为0.02%（0%-0.689%）的细胞识别突变的尖峰区域，而0.039%（0%-3.57%）的细胞对等效的未突变区域有反应，减少了49%。然而，对全长蛋白肽库的总体反应性在很大程度上保持不变（估计为87%）。不同疫苗接种或感染史的参与者在免疫识别丧失方面没有显著差异。这项针对意大利免疫成人的队列研究发现，尽管刺突蛋白发生突变，但SARS-CoV-2 Omicron变体仍被免疫系统的细胞成分识别。有理由认为，对住院和严重疾病的保护将继续维持。
What is the cellular immunity associated with the Omicron variant of SARS-CoV-2 among immunized individuals? In this cohort study among 61 individuals who had been vaccinated against COVID-19, cellular responses to the mutated regions of the Omicron spike protein were detected in 80% of participants. The mutations were associated with significantly reduced T-cell recognition compared with the vaccine strain, while reactivity to the whole spike protein was present in 100% of participants, and the proportion of remaining immunity to SARS-CoV-2 was estimated to be 87%. These findings suggest that cellular immunity to the Omicron variant was maintained despite the mutations in its spike protein; thus, immunization may confer protection from severe COVID-19 from the Omicron variant. This cohort study assesses T-cell reactivity to the Omicron variant of SARS-CoV-2 in individuals vaccinated against SARS-CoV-2. The emergence of the highly contagious Omicron variant of SARS-CoV-2 and the findings of a significantly reduced neutralizing potency of sera from individuals with previous SARS-CoV-2 infection or vaccination highlights the importance of studying cellular immunity to estimate the degree of immune protection to the new SARS-CoV-2 variant. To determine T-cell reactivity to the Omicron variant in individuals with established (natural and/or vaccine-induced) immunity to SARS-CoV-2. This was a cohort study conducted between December 20 and 21, 2021, at the Santa Lucia Foundation Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy, among health care worker and scientist volunteers. Lymphocytes from freshly drawn blood samples were isolated and immediately tested for reactivity to the spike protein of SARS-CoV-2. The main outcomes were the measurement of T-cell reactivity to the mutated regions of the spike protein of the Omicron BA.1 SARS-CoV-2 variant and the assessment of remaining T-cell immunity to the spike protein by stimulation with peptide libraries. A total of 61 volunteers (mean (range) age, 41.62 (21-62) years; 38 women [62%]) with different vaccination and SARS-CoV-2 infection backgrounds were enrolled. The median (range) frequency of CD4+ T cells reactive to peptides covering the mutated regions in the Omicron variant was 0.039% (0%-2.356%), a decrease of 64% compared with the frequency of CD4+ cells specific for the same regions of the ancestral strain (0.109% [0%-2.376%]). Within CD8+ T cells, a median (range) of 0.02% (0%-0.689%) of cells recognized the mutated spike regions, while 0.039% (0%-3.57%) of cells were reactive to the equivalent unmutated regions, a reduction of 49%. However, overall reactivity to the peptide library of the full-length protein was largely maintained (estimated 87%). No significant differences in loss of immune recognition were identified between groups of participants with different vaccination or infection histories. This cohort study of immunized adults in Italy found that despite the mutations in the spike protein, the SARS-CoV-2 Omicron variant was recognized by the cellular component of the immune system. It is reasonable to assume that protection from hospitalization and severe disease will be maintained.
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影响因子：
64.8
作者：
Liu J;Chandrashekar A;Sellers D;Barrett J;Jacob-Dolan C;Lifton M;McMahan K;Sciacca M;VanWyk H;Wu C;Yu J;Collier AY;Barouch DH
通讯作者：
Barouch DH
影响因子：
82.9
作者：
Gao Y;Cai C;Grifoni A;Müller TR;Niessl J;Olofsson A;Humbert M;Hansson L;Österborg A;Bergman P;Chen P;Olsson A;Sandberg JK;Weiskopf D;Price DA;Ljunggren HG;Karlsson AC;Sette A;Aleman S;Buggert M
通讯作者：
Buggert M
影响因子：
64.8
作者：
Oberhardt V;Luxenburger H;Kemming J;Schulien I;Ciminski K;Giese S;Csernalabics B;Lang-Meli J;Janowska I;Staniek J;Wild K;Basho K;Marinescu MS;Fuchs J;Topfstedt F;Janda A;Sogukpinar O;Hilger H;Stete K;Emmerich F;Bengsch B;Waller CF;Rieg S;Sagar;Boettler T;Zoldan K;Kochs G;Schwemmle M;Rizzi M;Thimme R;Neumann-Haefelin C;Hofmann M
通讯作者：
Hofmann M
影响因子：
24.8
作者：
GeurtsvanKessel CH;Geers D;Schmitz KS;Mykytyn AZ;Lamers MM;Bogers S;Scherbeijn S;Gommers L;Sablerolles RSG;Nieuwkoop NN;Rijsbergen LC;van Dijk LLA;de Wilde J;Alblas K;Breugem TI;Rijnders BJA;de Jager H;Weiskopf D;van der Kuy PHM;Sette A;Koopmans MPG;Grifoni A;Haagmans BL;de Vries RD
通讯作者：
de Vries RD
影响因子：
64.5
作者：
Tarke A;Coelho CH;Zhang Z;Dan JM;Yu ED;Methot N;Bloom NI;Goodwin B;Phillips E;Mallal S;Sidney J;Filaci G;Weiskopf D;da Silva Antunes R;Crotty S;Grifoni A;Sette A
通讯作者：
Sette A