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

Reincke, S. M.; Yuan, M.; Kornau, H.-C.; Corman, V. M.; van Hoof, S.; Sanchez-Sendin, E.; Ramberger, M.; Yu, W.; Hua, Y.; Tien, H.; Schmidt, M. L.; Schwarz, T.; Jeworowski, L. M.; Brandl, S. E.; Foverskov Rasmussen, H.; Homeyer, M. A.; Stöffler, L.; Barner, M.; Kunkel, D.; Huo, S.; Horler, J.; Wardenburg, N. v.; Kroidl, I.; Eser, T. M.; Wieser, A.; Geldmacher, C.; Hoelscher, M.; Gänzer, H.; Weiss, G.; Schmitz, D.; Drosten, C.; Prüss, H.; Wilson, I. A.; Kreye, J.

doi:10.1101/2021.09.30.462420

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bioRxiv · 10.1101/2021.09.30.462420

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

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Abstract

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 summarySARS-CoV-2 Beta variant elicits lineage-specific antibodies and antibodies with neutralizing breadth against wild-type virus and VOCs.

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Reincke, S. M., Yuan, M., Kornau, H.-C., Corman, V. M., van Hoof, S., Sanchez-Sendin, E., Ramberger, M., Yu, W., Hua, Y., Tien, H., Schmidt, M. L., Schwarz, T., Jeworowski, L. M., Brandl, S. E., Foverskov Rasmussen, H., Homeyer, M. A., Stöffler, L., Barner, M., Kunkel, D., Huo, S., Horler, J., Wardenburg, N. v., Kroidl, I., Eser, T. M., Wieser, A., Geldmacher, C., Hoelscher, M., Gänzer, H., Weiss, G., Schmitz, D., Drosten, C., Prüss, H., Wilson, I. A., Kreye, J.. 2021-09-30. SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies. https://doi.org/10.1101/2021.09.30.462420

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