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TitleStructural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2.
Journal, issue, pagesEmerg Microbes Infect, Vol. 12, Issue 1, Page 2146538, Year 2023
Publish dateJan 5, 2023
AuthorsMengxiao Luo / Biao Zhou / Eswar R Reddem / Bingjie Tang / Bohao Chen / Runhong Zhou / Hang Liu / Lihong Liu / Phinikoula S Katsamba / Ka-Kit Au / Hiu-On Man / Kelvin Kai-Wang To / Kwok-Yung Yuen / Lawrence Shapiro / Shangyu Dang / David D Ho / Zhiwei Chen /
PubMed AbstractIncreasing spread by SARS-CoV-2 Omicron variants challenges existing vaccines and broadly reactive neutralizing antibodies (bNAbs) against COVID-19. Here we determine the diversity, potency, breadth ...Increasing spread by SARS-CoV-2 Omicron variants challenges existing vaccines and broadly reactive neutralizing antibodies (bNAbs) against COVID-19. Here we determine the diversity, potency, breadth and structural insights of bNAbs derived from memory B cells of BNT162b2-vaccinee after homogeneous Omicron BA.1 breakthrough infection. The infection activates diverse memory B cell clonotypes for generating potent class I/II and III bNAbs with new epitopes mapped to the receptor-binding domain (RBD). The top eight bNAbs neutralize wildtype and BA.1 potently but display divergent IgH/IgL sequences and neuralization profiles against other variants of concern (VOCs). Two of them (P2D9 and P3E6) belonging to class III NAbs display comparable potency against BA.4/BA.5, although structural analysis reveals distinct modes of action. P3E6 neutralizes all variants tested through a unique bivalent interaction with two RBDs. Our findings provide new insights into hybrid immunity on BNT162b2-induced diverse memory B cells in response to Omicron breakthrough infection for generating diverse bNAbs with distinct structural basis.
External linksEmerg Microbes Infect / PubMed:36354024 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.2 - 4 Å
Structure data

27775

8dxs

EMDB-27775: Cryo-EM structure of RBD-directed neutralizing antibody P2B4 incomplex with prefusion SARS-CoV-2 spike glycoprotein
PDB-8dxs: Cryo-EM structure of RBD-directed neutralizing antibody P2B4 in complex with prefusion SARS-CoV-2 spike glycoprotein
Method: EM (single particle) / Resolution: 3.76 Å

33892

7ykj

EMDB-33892: Omicron spike trimer bound with P3E6 (Local Refinement)
PDB-7ykj: Omicron RBDs bound with P3E6 Fab (one up and one down)
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-33893: Omicron Spike trimer bound with up P3E6 Fab (2 RBDs up and 1 RBD down)
Method: EM (single particle) / Resolution: 3.25 Å

EMDB-33894: Omicron Spike trimer bound with side P3E6 Fab (1 RBD up and 2 RBDs down)
Method: EM (single particle) / Resolution: 3.27 Å

PDB-8dw9:
Crystal structure of neutralizing antibody D29 Fab in complex with SARS-CoV-2 spike receptor binding domain (RBD)
Method: X-RAY DIFFRACTION / Resolution: 4 Å

PDB-8dwa:
Crystal structure of neutralizing antibody P1D9 Fab in complex with SARS-CoV-2 spike receptor binding domain (RBD)
Method: X-RAY DIFFRACTION / Resolution: 3.2 Å

Chemicals

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

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / COVID-19 / P3E6 / Omicron / spike protein / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / SarbecoVirus / WIV1 RBD / Spike glycoprotein / Receptor Binding Protein / Neutralizing antibody / potent / 10-40 / Fab / SARS-CoV-2 / RBD / 10-28 / Fusion protein / RBD-directed antibody / P2B4 / IMMUNE SYSTEM

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