Induction of cross-reactive antibody responses against the RBD domain of the spike protein of SARS-CoV-2 by commensal microbiota

Ninnemann, J.; Budzinski, L.; Bondareva, M.; Witkowski, M.; Angermair, S.; Kreye, J.; Durek, P.; Reincke, M.; Sanchez-Sendin, E.; Yilmaz, S.; Sempert, T.; Heinz, G. A.; Tizian, C.; Raftery, M.; Schoenrich, G.; Matyushkina, D.; Smirnov, I.; Govorun, V.; Schrezenmeier, E. V.; Doerner, T.; Zocche, S.; Viviano, E.; Sehmsdorf, K. J.; Chang, H.-D.; Enghard, P.; Treskatsch, S.; Radbruch, A.; Diefenbach, A.; Pruess, H.; Mashreghi, M.-F.; Kruglov, A.

doi:10.1101/2021.08.08.455272

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bioRxiv · 10.1101/2021.08.08.455272

Induction of cross-reactive antibody responses against the RBD domain of the spike protein of SARS-CoV-2 by commensal microbiota

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Abstract

The commensal microflora is a source for multiple antigens that may induce cross-reactive antibodies against host proteins and pathogens. However, whether commensal bacteria can induce cross-reactive antibodies against SARS-CoV-2 remains unknown. Here we report that several commensal bacteria contribute to the generation of cross-reactive IgA antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. We identified SARS-CoV-2 unexposed individuals with RBD-binding IgA antibodies at their mucosal surfaces. Conversely, neutralising monoclonal anti-RBD antibodies recognised distinct commensal bacterial species. Some of these bacteria, such as Streptococcus salivarius, induced a cross-reactive anti-RBD antibodies upon supplementation in mice. Conversely, severely ill COVID-19 patients showed reduction of Streptococcus and Veillonella in their oropharynx and feces and a reduction of anti-RBD IgA at mucosal surfaces. Altogether, distinct microbial species of the human microbiota can induce secretory IgA antibodies cross-reactive for the RBD of SARS-CoV-2.

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Ninnemann, J., Budzinski, L., Bondareva, M., Witkowski, M., Angermair, S., Kreye, J., Durek, P., Reincke, M., Sanchez-Sendin, E., Yilmaz, S., Sempert, T., Heinz, G. A., Tizian, C., Raftery, M., Schoenrich, G., Matyushkina, D., Smirnov, I., Govorun, V., Schrezenmeier, E. V., Doerner, T., Zocche, S., Viviano, E., Sehmsdorf, K. J., Chang, H.-D., Enghard, P., Treskatsch, S., Radbruch, A., Diefenbach, A., Pruess, H., Mashreghi, M.-F., Kruglov, A.. 2021-08-08. Induction of cross-reactive antibody responses against the RBD domain of the spike protein of SARS-CoV-2 by commensal microbiota. https://doi.org/10.1101/2021.08.08.455272

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