SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies
S. Momsen Reincke, Meng Yuan, Hans‐Christian Kornau, Victor M. Corman, Scott van Hoof, Elisa Sánchez-Sendín, Melanie Ramberger, Wenli Yu, Yuanzi Hua, Henry J. Tien, Marie Luisa Schmidt, Tatjana Schwarz, Lara M. Jeworowski, Sarah Brandl, Helle Foverskov Rasmussen, Marie A. Homeyer, Laura Stöffler, Martin Barner, Désirée Kunkel, Shufan Huo, Johannes Horler, Niels von Wardenburg, Inge Kroidl, Tabea M. Eser, Andreas Wieser, Christof Geldmacher, Michael Höelscher, Hannes Gänzer, Günter Weiß, Dietmar Schmitz, Christian Drosten, Harald Prüß, Ian A. Wilson, Jakob Kreye
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. In this study, serum of Beta-infected patients revealed reduced cross-neutralization of wild-type virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wild type-elicited antibodies, including a public VH1-58 clonotype that targets the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift, with implications for design of next-generation vaccines and therapeutics.