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Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines

Cao, Yunlong ; Yisimayi, Ayijiang ; Bai, Yali ; Huang, Weijin ; Li, Xiaofeng ; Zhang, Zhiying ; Yuan, Tianjiao ; An, Ran ; Wang, Jing ; Xiao, Tianhe ; Du, Shuo ; Ma, Wenping ; Song, Liyang ; Li, Yongzheng ; Li, Xiang ; Song, Weiliang ; Wu, Jiajing ; Liu, Shuo ; Li, Xuemei ; Zhang, Yonghong ; Su, Bin ; Guo, Xianghua ; Wei, Yangyang ; Gao, Chuanping ; Zhang, Nana ; Zhang, Yifei ; Dou, Yang ; Xu, Xiaoyu ; Shi, Rui ; Lu, Bai ; Jin, Ronghua ; Ma, Yingmin ; Qin, Chengfeng ; Wang, Youchun ; Feng, Yingmei ; Xiao, Junyu ; Xie, Xiaoliang Sunney

Cell research, 2021-07, Vol.31 (7), p.732-741 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines
Autor: Cao, Yunlong ; Yisimayi, Ayijiang ; Bai, Yali ; Huang, Weijin ; Li, Xiaofeng ; Zhang, Zhiying ; Yuan, Tianjiao ; An, Ran ; Wang, Jing ; Xiao, Tianhe ; Du, Shuo ; Ma, Wenping ; Song, Liyang ; Li, Yongzheng ; Li, Xiang ; Song, Weiliang ; Wu, Jiajing ; Liu, Shuo ; Li, Xuemei ; Zhang, Yonghong ; Su, Bin ; Guo, Xianghua ; Wei, Yangyang ; Gao, Chuanping ; Zhang, Nana ; Zhang, Yifei ; Dou, Yang ; Xu, Xiaoyu ; Shi, Rui ; Lu, Bai ; Jin, Ronghua ; Ma, Yingmin ; Qin, Chengfeng ; Wang, Youchun ; Feng, Yingmei ; Xiao, Junyu ; Xie, Xiaoliang Sunney
Assuntos: Animals ; Antibodies ; Antibodies, Neutralizing - blood ; Antibodies, Neutralizing - immunology ; Antigens ; Cell Line ; Complementarity ; Conformation ; COVID-19 - blood ; COVID-19 - immunology ; COVID-19 - prevention & control ; COVID-19 vaccines ; COVID-19 Vaccines - immunology ; COVID-19 Vaccines - pharmacology ; Deactivation ; Domains ; HEK293 Cells ; Humans ; Immune response ; Immune response (humoral) ; Immune system ; Immunity, Humoral ; Immunological tolerance ; Leukocytes (mononuclear) ; Models, Molecular ; Mutation ; Neutralization ; Neutralizing ; Peripheral blood mononuclear cells ; SARS-CoV-2 - genetics ; SARS-CoV-2 - immunology ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Spike Glycoprotein, Coronavirus - genetics ; Spike Glycoprotein, Coronavirus - immunology ; Vaccines ; Vaccines, Inactivated - immunology ; Vaccines, Inactivated - pharmacology ; Vaccines, Subunit - immunology ; Vaccines, Subunit - pharmacology
É parte de: Cell research, 2021-07, Vol.31 (7), p.732-741
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Descrição: 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.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines

England: Nature Publishing Group

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