Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2
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 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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
Emerging Microbes and Infections - 12(2023), 1 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mengxiao Luo [VerfasserIn] |
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| Links: |
doi.org [kostenfrei] |
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| Themen: |
Broadly neutralizing antibody |
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| doi: |
10.1080/22221751.2022.2146538 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
DOAJ000165506 |
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| 520 | |a 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 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. | ||
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Omicron BA.1 breakthrough infection | |
| 650 | 4 | |a hybrid immunity | |
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| 650 | 4 | |a memory B cell | |
| 650 | 4 | |a structural basis of antibody | |
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| 700 | 0 | |a Eswar R. Reddem |e verfasserin |4 aut | |
| 700 | 0 | |a Bingjie Tang |e verfasserin |4 aut | |
| 700 | 0 | |a Bohao Chen |e verfasserin |4 aut | |
| 700 | 0 | |a Runhong Zhou |e verfasserin |4 aut | |
| 700 | 0 | |a Hang Liu |e verfasserin |4 aut | |
| 700 | 0 | |a Lihong Liu |e verfasserin |4 aut | |
| 700 | 0 | |a Phinikoula S. Katsamba |e verfasserin |4 aut | |
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| 700 | 0 | |a Kwok-Yung Yuen |e verfasserin |4 aut | |
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| 700 | 0 | |a Shangyu Dang |e verfasserin |4 aut | |
| 700 | 0 | |a David D. Ho |e verfasserin |4 aut | |
| 700 | 0 | |a Zhiwei Chen |e verfasserin |4 aut | |
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