Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2

Mengxiao 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

doi:10.1080/22221751.2022.2146538

Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2

Mengxiao 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

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

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.

Original language	English
Article number	2146538
Journal	Emerging Microbes and Infections
Volume	12
Issue number	1
DOIs	https://doi.org/10.1080/22221751.2022.2146538
Publication status	Published - 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

ASJC Scopus Subject Areas

Epidemiology
Parasitology
Microbiology
Immunology
Drug Discovery
Infectious Diseases
Virology

Keywords

broadly neutralizing antibody
hybrid immunity
memory B cell
Omicron BA.1 breakthrough infection
SARS-CoV-2
structural basis of antibody

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10.1080/22221751.2022.2146538

Cite this

Luo, M., Zhou, B., Reddem, E. R., Tang, B., Chen, B., Zhou, R., Liu, H., Liu, L., Katsamba, P. S., Au, K. K., Man, H. O., To, K. K. W., Yuen, K. Y., Shapiro, L., Dang, S., Ho, D. D., & Chen, Z. (2023). Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2. Emerging Microbes and Infections, 12(1), Article 2146538. https://doi.org/10.1080/22221751.2022.2146538

Luo, M, Zhou, B, Reddem, ER, Tang, B, Chen, B, Zhou, R, Liu, H, Liu, L, Katsamba, PS, Au, KK, Man, HO, To, KKW, Yuen, KY, Shapiro, L, Dang, S, Ho, DD & Chen, Z 2023, 'Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2', Emerging Microbes and Infections, vol. 12, no. 1, 2146538. https://doi.org/10.1080/22221751.2022.2146538

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Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Keywords

Access to Document

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