Antibody feedback contributes to facilitating the development of Omicron-reactive memory B cells in SARS-CoV-2 mRNA vaccinees
© 2022 Inoue et al..
In contrast to a second dose of the SARS-CoV-2 mRNA vaccine, a third dose elicits potent neutralizing activity against the Omicron variant. To address the underlying mechanism for this differential antibody response, we examined spike receptor-binding domain (RBD)-specific memory B cells in vaccinated individuals. Frequency of Omicron-reactive memory B cells increased ∼9 mo after the second vaccine dose. These memory B cells show an altered distribution of epitopes from pre-second memory B cells, presumably due to an antibody feedback mechanism. This hypothesis was tested using mouse models, showing that an addition or a depletion of RBD-induced serum antibodies results in a concomitant increase or decrease, respectively, of Omicron-reactive germinal center (GC) and memory B cells. Our data suggest that pre-generated antibodies modulate the selection of GC and subsequent memory B cells after the second vaccine dose, accumulating more Omicron-reactive memory B cells over time, which contributes to the generation of Omicron-neutralizing antibodies elicited by the third vaccine dose.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:220 |
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Enthalten in: |
The Journal of experimental medicine - 220(2023), 2 vom: 06. Feb. |
Sprache: |
Englisch |
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Beteiligte Personen: |
Inoue, Takeshi [VerfasserIn] |
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Links: |
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Themen: |
Antibodies, Neutralizing |
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Anmerkungen: |
Date Completed 15.12.2022 Date Revised 13.06.2023 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1084/jem.20221786 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM350241066 |
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520 | |a In contrast to a second dose of the SARS-CoV-2 mRNA vaccine, a third dose elicits potent neutralizing activity against the Omicron variant. To address the underlying mechanism for this differential antibody response, we examined spike receptor-binding domain (RBD)-specific memory B cells in vaccinated individuals. Frequency of Omicron-reactive memory B cells increased ∼9 mo after the second vaccine dose. These memory B cells show an altered distribution of epitopes from pre-second memory B cells, presumably due to an antibody feedback mechanism. This hypothesis was tested using mouse models, showing that an addition or a depletion of RBD-induced serum antibodies results in a concomitant increase or decrease, respectively, of Omicron-reactive germinal center (GC) and memory B cells. Our data suggest that pre-generated antibodies modulate the selection of GC and subsequent memory B cells after the second vaccine dose, accumulating more Omicron-reactive memory B cells over time, which contributes to the generation of Omicron-neutralizing antibodies elicited by the third vaccine dose | ||
650 | 4 | |a Journal Article | |
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700 | 1 | |a Shinnakasu, Ryo |e verfasserin |4 aut | |
700 | 1 | |a Kawai, Chie |e verfasserin |4 aut | |
700 | 1 | |a Yamamoto, Hiromi |e verfasserin |4 aut | |
700 | 1 | |a Sakakibara, Shuhei |e verfasserin |4 aut | |
700 | 1 | |a Ono, Chikako |e verfasserin |4 aut | |
700 | 1 | |a Itoh, Yumi |e verfasserin |4 aut | |
700 | 1 | |a Terooatea, Tommy |e verfasserin |4 aut | |
700 | 1 | |a Yamashita, Kazuo |e verfasserin |4 aut | |
700 | 1 | |a Okamoto, Toru |e verfasserin |4 aut | |
700 | 1 | |a Hashii, Noritaka |e verfasserin |4 aut | |
700 | 1 | |a Ishii-Watabe, Akiko |e verfasserin |4 aut | |
700 | 1 | |a Butler, Noah S |e verfasserin |4 aut | |
700 | 1 | |a Matsuura, Yoshiharu |e verfasserin |4 aut | |
700 | 1 | |a Matsumoto, Hisatake |e verfasserin |4 aut | |
700 | 1 | |a Otsuka, Shinya |e verfasserin |4 aut | |
700 | 1 | |a Hiraoka, Kei |e verfasserin |4 aut | |
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700 | 1 | |a Murakami, Masaaki |e verfasserin |4 aut | |
700 | 1 | |a Kurosaki, Tomohiro |e verfasserin |4 aut | |
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