Antibody feedback contributes to facilitating the development of Omicron-reactive memory B cells in SARS-CoV-2 mRNA vaccinees

Takeshi Inoue; Ryo Shinnakasu; Chie Kawai; Hiromi Yamamoto; Shuhei Sakakibara; Chikako Ono; Yumi Itoh; Tommy Terooatea; Kazuo Yamashita; Toru Okamoto; Noritaka Hashii; Akiko Ishii-Watabe; Noah S Butler; Yoshiharu Matsuura; Hisatake Matsumoto; Shinya Otsuka; Kei Hiraoka; Takanori Teshima; Masaaki Murakami; Tomohiro Kurosaki

doi:10.1084/jem.20221786

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Antibody feedback contributes to facilitating the development of Omicron-reactive memory B cells in SARS-CoV-2 mRNA vaccinees

Takeshi Inoue, Ryo Shinnakasu, Chie Kawai, Hiromi Yamamoto, Shuhei Sakakibara, Chikako Ono, Yumi Itoh, Tommy Terooatea, Kazuo Yamashita, Toru Okamoto, …

The Journal of experimental medicine, Vol.220(2), e20221786

02/06/2023

DOI: 10.1084/jem.20221786

PMCID: PMC9750191

PMID: 36512034

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Abstract

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.

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Title: Subtitle: Antibody feedback contributes to facilitating the development of Omicron-reactive memory B cells in SARS-CoV-2 mRNA vaccinees
Creators: Takeshi Inoue - The University of Osaka
Ryo Shinnakasu - Ehime University Hospital
Chie Kawai - The University of Osaka
Hiromi Yamamoto - The University of Osaka
Shuhei Sakakibara - The University of Osaka
Chikako Ono - The University of Osaka
Yumi Itoh - The University of Osaka
Tommy Terooatea - KOTAI Biotechnologies, Inc., Osaka, Japan
Kazuo Yamashita - KOTAI Biotechnologies, Inc., Osaka, Japan
Toru Okamoto - The University of Osaka
Noritaka Hashii - Biologicals (Czechia)
Akiko Ishii-Watabe - Biologicals (Czechia)
Noah S Butler - Department of Microbiology and Immunology, The University of Iowa, Iowa City, IA, USA
Yoshiharu Matsuura - The University of Osaka
Hisatake Matsumoto - The University of Osaka
Shinya Otsuka - Hakodate National Hospital
Kei Hiraoka - Hakodate National Hospital
Takanori Teshima - Hokkaido University
Masaaki Murakami - National Institute for Physiological Sciences
Tomohiro Kurosaki - RIKEN Center for Integrative Medical Sciences
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.220(2), e20221786
DOI: 10.1084/jem.20221786
PMID: 36512034
PMCID: PMC9750191
NLM abbreviation: J Exp Med
ISSN: 0022-1007
eISSN: 1540-9538
Grant note: JP22gm1810004 / Japan Agency for Medical Research and Development JP21H02749 / Japan Society for the Promotion of Science JPMXS0120330644 / Quantum LEAP Flagship Program
Language: English
Date published: 02/06/2023
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology
Record Identifier: 9984327059502771

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