Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines
| العنوان: | Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines |
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| المؤلفون: | Yongzheng Li, Jiajing Wu, Xiaoyu Xu, Ran An, Xiaoliang Sunney Xie, Rui Shi, Na-Na Zhang, Chuanping Gao, Liyang Song, Yingmin Ma, Ayijiang Yisimayi, Xuemei Li, Yali Bai, Y Cao, Youchun Wang, Tianhe Xiao, Shuo Du, Yangyang Wei, Yifei Zhang, Wenping Ma, Xiang Li, Junyu Xiao, Weiliang Song, Cheng-Feng Qin, Bin Su, Shuo Liu, Jing Wang, Zhiying Zhang, Xiaofeng Li, Tianjiao Yuan, Ronghua Jin, Yingmei Feng, Yang Dou, Yonghong Zhang, Bai Lu, Weijin Huang, Xianghua Guo |
| المصدر: | Cell Research |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Immunology, Complementarity determining region, medicine.disease_cause, Article, Neutralization, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Cryoelectron microscopy, Neutralization Tests, Immunity, medicine, Humans, Molecular Biology, X-ray crystallography, 030304 developmental biology, 0303 health sciences, Mutation, biology, SARS-CoV-2, COVID-19, Cell Biology, Antibodies, Neutralizing, Virology, Inactivated vaccine, biology.protein, Antibody, 030217 neurology & neurosurgery |
| الوصف: | SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) and natural infection. Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause. VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions. In contrast, the 242–244 deletion (242–244Δ) would abolish most neutralization activity of anti-NTD NAbs by interrupting the conformation of NTD antigenic supersite, indicating a much less diversity of anti-NTD NAbs than anti-RBD NAbs. Plasma of convalescents and CoronaVac vaccinees displayed comparable neutralization reductions against pseudo- and authentic 501Y.V2 variants, mainly caused by E484K/N501Y and 242–244Δ, with the effects being additive. Importantly, RBD-subunit vaccinees exhibit markedly higher tolerance to 501Y.V2 than convalescents, since the elicited anti-RBD NAbs display a high diversity and are unaffected by NTD mutations. Moreover, an extended gap between the third and second doses of ZF2001 leads to better neutralizing activity and tolerance to 501Y.V2 than the standard three-dose administration. Together, these results suggest that the deployment of RBD-vaccines, through a third-dose boost, may be ideal for combating SARS-CoV-2 variants when necessary, especially for those carrying mutations that disrupt the NTD supersite. |
| تدمد: | 1748-7838 1001-0602 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0cc6da328c967b8d310b738c681960ad https://doi.org/10.1038/s41422-021-00514-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0cc6da328c967b8d310b738c681960ad |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17487838 10010602 |
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