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TitleHumoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines.
Journal, issue, pagesCell Res, Vol. 31, Issue 7, Page 732-741, Year 2021
Publish dateMay 21, 2021
AuthorsYunlong Cao / Ayijiang Yisimayi / Yali Bai / Weijin Huang / Xiaofeng Li / Zhiying Zhang / Tianjiao Yuan / Ran An / Jing Wang / Tianhe Xiao / Shuo Du / Wenping Ma / Liyang Song / Yongzheng Li / Xiang Li / Weiliang Song / Jiajing Wu / Shuo Liu / Xuemei Li / Yonghong Zhang / Bin Su / Xianghua Guo / Yangyang Wei / Chuanping Gao / Nana Zhang / Yifei Zhang / Yang Dou / Xiaoyu Xu / Rui Shi / Bai Lu / Ronghua Jin / Yingmin Ma / Chengfeng Qin / Youchun Wang / Yingmei Feng / Junyu Xiao / Xiaoliang Sunney Xie /
PubMed AbstractSARS-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 ...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.
External linksCell Res / PubMed:34021265 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.41 - 3.18 Å
Structure data

EMDB-31014, PDB-7e8c:
SARS-CoV-2 S-6P in complex with 9 Fabs
Method: EM (single particle) / Resolution: 3.16 Å

EMDB-31017, PDB-7e8f:
SARS-CoV-2 NTD in complex with N9 Fab
Method: EM (single particle) / Resolution: 3.18 Å

PDB-7e7x:
SARS-CoV-2 Spike Protein N terminal domain in Complex with N11 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.78 Å

PDB-7e7y:
Crystal structure of the SARS-CoV-2 S RBD in complex with BD-623 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.41 Å

PDB-7e86:
Crystal structure of the SARS-CoV-2 S RBD in complex with BD-508 Fab
Method: X-RAY DIFFRACTION / Resolution: 2.9 Å

PDB-7e88:
Crystal structure of the SARS-CoV-2 S RBD in complex with BD-515 Fab
Method: X-RAY DIFFRACTION / Resolution: 3.14 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
  • SARS coronavirus Tor2
KeywordsVIRAL PROTEIN / SARS-CoV-2 / Spike / NTD / Antibody / Spike RBD Antibody / IMMUNE SYSTEM / Complex

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