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TitleA proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2.
Journal, issue, pagesNatl Sci Rev, Vol. 8, Issue 8, Page nwab053, Year 2021
Publish dateMar 27, 2021
AuthorsLi Zhang / Lei Cao / Xing-Su Gao / Bin-Yang Zheng / Yong-Qiang Deng / Jing-Xin Li / Rui Feng / Qian Bian / Xi-Ling Guo / Nan Wang / Hong-Ying Qiu / Lei Wang / Zhen Cui / Qing Ye / Geng Chen / Kui-Kui Lu / Yin Chen / Yu-Tao Chen / Hong-Xing Pan / Jiaping Yu / Wenrong Yao / Bao-Li Zhu / Jianping Chen / Yong Liu / Cheng-Feng Qin / Xiangxi Wang / Feng-Cai Zhu /
PubMed AbstractMutations and transient conformational movements of the receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory ...Mutations and transient conformational movements of the receptor binding domain (RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To mitigate viral escape, we developed a cocktail of neutralizing antibodies (NAbs) targeting epitopes located on different domains of spike (S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting the N-terminal domain (NTD) and RBD domain of S, effective at concentrations. Remarkably, a combination of RBD-targeting NAbs and NTD-binding NAbs, FC05, enhanced the neutralization potency in cell-based assays and an animal model. Results of competitive surface plasmon resonance assays and cryo-electron microscopy (cryo-EM) structures of antigen-binding fragments bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in the NTD and RBD of S, when immunized in rabbits and macaques, elicited potent protective immune responses against SARS-CoV-2. More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.
External linksNatl Sci Rev / PubMed:34676098 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 3.9 Å
Structure data

30573

7d4g

EMDB-30573, PDB-7d4g:
A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2
Method: EM (single particle) / Resolution: 3.9 Å

30895

7dx4

EMDB-30895, PDB-7dx4:
The structure of FC08 Fab-hA.CE2-RBD complex
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV-2 / Spike / antibody / neutralizing antibody / hACE2 / RBD

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