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

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 O...

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Main Authors: 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
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2022.2146538
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Summary: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.
ISSN:2222-1751