SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

Reincke, S Momsen; Yuan, Meng; Kornau, Hans-Christian; Corman, Victor M; van Hoof, Scott; Sánchez-Sendin, Elisa; Ramberger, Melanie; Yu, Wenli; Hua, Yuanzi; Tien, Henry; Schmidt, Marie Luisa; Schwarz, Tatjana; Jeworowski, Lara Maria; Brandl, Sarah E; Rasmussen, Helle Foverskov; Homeyer, Marie A; Stöffler, Laura; Barner, Martin; Kunkel, Désirée; Huo, Shufan; Horler, Johannes; von Wardenburg, Niels; Kroidl, Inge; Eser, Tabea M; Wieser, Andreas; Geldmacher, Christof; Hoelscher, Michael; Gänzer, Hannes; Weiss, Günter; Schmitz, Dietmar; Drosten, Christian; Prüss, Harald; Wilson, Ian A.; Kreye, Jakob

SARS-CoV-2 Beta variant of concern (VOC) resists neutralization by major classes of antibodies from non-VOC COVID-19 patients and vaccinated individuals. Here, serum of Beta variant infected patients revealed reduced cross-neutralization of non-VOC virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of novel VOC-specific clonotypes and accommodation of VOC-defining amino acids into a major non-VOC antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with non-VOC-elicited antibodies, including a public VH1-58 clonotype targeting the RBD ridge independent of VOC mutations. 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. One sentence summary SARS-CoV-2 Beta variant elicits lineage-specific antibodies and antibodies with neutralizing breadth against wild-type virus and VOCs.