Journal: Immunity / Year: 2022 Title: Analysis of memory B cells identifies conserved neutralizing epitopes on the N-terminal domain of variant SARS-Cov-2 spike proteins. Authors: Zijun Wang / Frauke Muecksch / Alice Cho / Christian Gaebler / Hans-Heinrich Hoffmann / Victor Ramos / Shuai Zong / Melissa Cipolla / Briana Johnson / Fabian Schmidt / Justin DaSilva / Eva ...Authors: Zijun Wang / Frauke Muecksch / Alice Cho / Christian Gaebler / Hans-Heinrich Hoffmann / Victor Ramos / Shuai Zong / Melissa Cipolla / Briana Johnson / Fabian Schmidt / Justin DaSilva / Eva Bednarski / Tarek Ben Tanfous / Raphael Raspe / Kaihui Yao / Yu E Lee / Teresia Chen / Martina Turroja / Katrina G Milard / Juan Dizon / Anna Kaczynska / Anna Gazumyan / Thiago Y Oliveira / Charles M Rice / Marina Caskey / Paul D Bieniasz / Theodora Hatziioannou / Christopher O Barnes / Michel C Nussenzweig / Abstract: SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal domain (NTD) of the ...SARS-CoV-2 infection or vaccination produces neutralizing antibody responses that contribute to better clinical outcomes. The receptor-binding domain (RBD) and the N-terminal domain (NTD) of the spike trimer (S) constitute the two major neutralizing targets for antibodies. Here, we use NTD-specific probes to capture anti-NTD memory B cells in a longitudinal cohort of infected individuals, some of whom were vaccinated. We found 6 complementation groups of neutralizing antibodies. 58% targeted epitopes outside the NTD supersite, 58% neutralized either Gamma or Omicron, and 14% were broad neutralizers that also neutralized Omicron. Structural characterization revealed that broadly active antibodies targeted three epitopes outside the NTD supersite including a class that recognized both the NTD and SD2 domain. Rapid recruitment of memory B cells producing these antibodies into the plasma cell compartment upon re-infection likely contributes to the relatively benign course of subsequent infections with SARS-CoV-2 variants, including Omicron.
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