TY - JOUR T1 - Induction of cross-reactive antibody responses against the RBD domain of the spike protein of SARS-CoV-2 by commensal microbiota JF - bioRxiv DO - 10.1101/2021.08.08.455272 SP - 2021.08.08.455272 AU - Justus Ninnemann AU - Lisa Budzinski AU - Marina Bondareva AU - Mario Witkowski AU - Stefan Angermair AU - Jakob Kreye AU - Pawel Durek AU - S. Momsen Reincke AU - Elisa Sánchez-Sendin AU - Selin Yilmaz AU - Toni Sempert AU - Gitta Anne Heinz AU - Caroline Tizian AU - Martin Raftery AU - Günther Schönrich AU - Daria Matyushkina AU - Ivan V. Smirnov AU - Vadim M. Govorun AU - Eva Schrezenmeier AU - Thomas Dörner AU - Silvia Zocche AU - Edoardo Viviano AU - Katharina Johanna Sehmsdorf AU - Hyun-Dong Chang AU - Philipp Enghard AU - Sascha Treskatsch AU - Andreas Radbruch AU - Andreas Diefenbach AU - Harald Prüss AU - Mir-Farzin Mashreghi AU - Andrey A. Kruglov Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/10/15/2021.08.08.455272.abstract N2 - 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.Competing Interest StatementJ.N., L. B., and A.K. have a pending patent application with regard to utilization of commensal bacteria for induction of antiviral immune responses. ER -