Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses
Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses
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三重疫苗接种个体中的 Omicron BA.1/BA.2 感染增强了多种粘膜和血液免疫反应
DOI：
10.1101/2023.01.28.23285084
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Hornsby H
中科院分区：
文献类型：
--
作者：
Hornsby H
SARS-CoV-2 Omicron变种明显的免疫逃逸导致大量通过接种疫苗和感染而产生的混合免疫个体。主要基于循环中和抗体(NAB)的数据，人们担心在三次接种的人中Omicron突破性感染导致Omicron特异性免疫诱导不良，特别是以前的SARS-CoV-2病史与严重的免疫抑制有关。采用更广泛和更全面的方法，我们研究了在BA.1/BA.2感染后，有和没有SARS-CoV-2感染病史的三重mRNA疫苗接种的个体的粘膜和血液对尖峰和非尖峰抗原的免疫。我们发现大多数个体在感染后增加了BA.1/BA.2/BA.5特异性的NAB，但证实了那些感染幼稚的人增加的幅度和Omicron后的滴度确实更高。相比之下，鼻腔抗体反应显著增加，与既往感染病史无关，包括对BA.5刺激物的中和活性。刺激性T细胞仅在感染未接种疫苗的人中增加；然而，在先前感染的人中，Omicron后的T细胞反应仍然显著较高，这些人在接种3rdmRNA疫苗后似乎具有最大限度的诱导反应，具有高细胞毒力的CD8+表型。对非尖峰抗原的抗体和T细胞反应也显著增加，无论以前的感染状态如何，在以前感染的人中可以看到对他们第一次感染启动的免疫力的增强。这些发现表明，由奥米克龙突破性感染诱导的混合免疫是高度动态、复杂和分区的，具有显著的免疫增强作用，有助于预防未来奥米克龙变种引起的新冠肺炎。
Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in large numbers of individuals with hybrid immunity, generated through a combination of vaccination and infection. Based primarily on circulating neutralizing antibody (NAb) data, concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that a history of prior SARS-CoV-2 in particular is associated with profound immune dampening. Taking a broader and comprehensive approach, we characterized mucosal and blood immunity to both spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without a history of previous SARS-CoV-2 infection. We find that the majority of individuals increase BA.1/BA.2/BA.5-specific NAb following infection, but confirm that the magnitude of increase and post-omicron titres are indeed higher in those who were infection-naive. In contrast, significant increases in nasal antibody responses are seen regardless of prior infection history, including neutralizing activity against BA.5 spike. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are still significantly higher in previously-infected individuals, who appear to have maximally induced responses with a CD8+ phenotype of high cytotoxic potential after their 3rdmRNA vaccine dose. Antibody and T cell responses to non-spike antigens also increase significantly regardless of prior infection status, with a boost seen in previously-infected individuals to immunity primed by their first infection. These findings suggest that hybrid immunity induced by omicron breakthrough infections is highly dynamic, complex, and compartmentalised, with significant immune enhancement that can help protect against COVID-19 caused by future omicron variants.
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DOI：
10.1126/science.abn8347
发表时间：
2022-03-25
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Elliott P;Bodinier B;Eales O;Wang H;Haw D;Elliott J;Whitaker M;Jonnerby J;Tang D;Walters CE;Atchison C;Diggle PJ;Page AJ;Trotter AJ;Ashby D;Barclay W;Taylor G;Ward H;Darzi A;Cooke GS;Chadeau-Hyam M;Donnelly CA
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Donnelly CA
DOI：
10.1056/nejmoa2119451
发表时间：
2022-04-21
期刊：
The New England journal of medicine
影响因子：
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作者：
Andrews N;Stowe J;Kirsebom F;Toffa S;Rickeard T;Gallagher E;Gower C;Kall M;Groves N;O'Connell AM;Simons D;Blomquist PB;Zaidi A;Nash S;Iwani Binti Abdul Aziz N;Thelwall S;Dabrera G;Myers R;Amirthalingam G;Gharbia S;Barrett JC;Elson R;Ladhani SN;Ferguson N;Zambon M;Campbell CNJ;Brown K;Hopkins S;Chand M;Ramsay M;Lopez Bernal J
通讯作者：
Lopez Bernal J
DOI：
10.1126/science.abq0203
发表时间：
2022-08-19
期刊：
Science (New York, N.Y.)
影响因子：
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DOI：
10.1038/s41577-022-00678-4
发表时间：
2022-03
期刊：
Nature reviews. Immunology
影响因子：
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作者：
Sigal A
通讯作者：
Sigal A
英国普通人群第三次/加强疫苗接种或突破性感染后针对 SARS-CoV-2 Omicron 变体的保护与抗尖峰抗体反应的相关性
DOI：
--
发表时间：
2022
期刊：
medRxiv
影响因子：
--
作者：
J. Wei;P. Matthews;N. Stoesser;J. Newton;I. Diamond;R. Studley;N. Taylor;J. Bell;J. Farrar;B. Marsden;J. Kolenchery;S. Hoosdally;Y. Jones;D. Stuart;D. Crook;T. Peto;A. Walker;K. Pouwels;D. Eyre
通讯作者：
D. Eyre