SARS-CoV-2 Omicron-neutralizing memory B cells are elicited by two doses of BNT162b2 mRNA vaccine.

Ryutaro Kotaki,Kunihiro Oba,Tadaki Suzuki,Hidefumi Shimizu,Kazutaka Terahara,Takayuki Matsumura,Taishi Onodera,Fukumi Nakamura-Uchiyama,Ayae Nishiyama,Shuetsu Fukushi,Yu Adachi,Keisuke Tonouchi,Lin Sun,Saya Moriyama,Tomohiro Takano,Masanori Isogawa,Takaki Nagakura,Masaharu Shinkai,Yoshimasa Takahashi

doi:10.1126/sciimmunol.abn8590

Abstract

Multiple SARS-CoV-2 variants possess mutations in the spike receptor-binding domain (RBD) with potential to evade neutralizing antibody. In particular, the Beta and Omicron variants escape from antibody neutralizing activity in those who received two doses of BNT162b2 mRNA vaccine. Nonetheless, boosting with a third vaccine dose or by breakthrough infection improves the overall breadth of the neutralizing antibodies, but the mechanism remains unclear. Here, we longitudinally profiled the cellular composition of RBD-binding memory B cell subsets and their antibody binding and neutralizing activity against SARS-CoV-2 variants following the second dose of mRNA vaccine. Two doses of the mRNA vaccine elicited plasma neutralizing antibodies with a limited activity against Beta and Omicron but induced an expanded antibody breadth overtime, up to 4.9 months post vaccination. In contrast, more than one third of RBD-binding IgG+ memory B cells with a resting phenotype initially bound the Beta and Omicron variants and steadily increased the B cell receptor (BCR) breadth overtime. As a result, a fraction of the resting memory B cell subset secreted Beta and Omicron-neutralizing antibody when stimulated in vitro. The neutralizing breadth of the resting memory B cell subset helps us understand the prominent recall of Omicron-neutralizing antibodies after an additional booster or breakthrough infection in fully vaccinated individuals.

Highlights

SARS-CoV-2 mRNA vaccination elicits long-lived plasma cells and memory B (Bmem) cells, which constitute two layers of the humoral protection against SARS-CoV-2 [1,2,3,4,5,6,7,8]
SARS-CoV-2 virus or viral antigens are recognized by the B cell receptor (BCR) of Bmem cells that differentiate into plasma cells as the second arm of humoral protection
We examined the breadth of Bmem cells against the Beta and Omicron variants and the temporal shift in the composition of the Bmem cell subsets over time in those who have received two doses of mRNA vaccine

Summary

Introduction

SARS-CoV-2 mRNA vaccination elicits long-lived plasma cells and memory B (Bmem) cells, which constitute two layers of the humoral protection against SARS-CoV-2 [1,2,3,4,5,6,7,8]. The preexisting antibodies provided by plasma cells prevent infection at the initial infection site and contribute to sterilizing immunity if they are present in sufficient amounts at the time of infection. Bmem cells remain in the peripheral blood without noticeable decline for up to six months after two mRNA vaccine doses [1, 2]. Robust humoral protection by persistent Bmem cells along with T-cell-mediated cellular immunity is suggested to prevent the onset of symptomatic or severe disease in vaccinees [10], likely contributing to the long-lasting vaccine effectiveness for preventing severe disease [10]

Methods

Results

Conclusion