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

• DOI: 10.1084/jem.20221786
• Publication Date: 2022-12-13T14:41:00Z
• Authors: 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
• Keywords: Memory B cell

In contrast to a second dose of the SARS-CoV-2 mRNA vaccine, third elicits potent neutralizing activity against Omicron variant. To address underlying mechanism for this differential antibody response, we examined spike receptor-binding domain (RBD)–specific memory B cells in vaccinated individuals. Frequency Omicron-reactive increased ∼9 mo after vaccine dose. These show an altered distribution epitopes from pre-second cells, presumably due feedback mechanism. This hypothesis was tested using mouse models, showing that addition or depletion RBD-induced serum antibodies results concomitant increase decrease, respectively, germinal center (GC) and cells. Our data suggest pre-generated modulate selection GC subsequent dose, accumulating more over time, which contributes generation Omicron-neutralizing elicited by