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© Research
Publication : Cell host & microbe

Cross-regulation of antibody responses against the SARS-CoV-2 Spike protein and commensal microbiota via molecular mimicry.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell host & microbe - 08 Nov 2023

Ninnemann J, Bondareva M, Budzinski L, Durek P, Witkowski M, Angermair S, Kreye J, Letz P, Ferreira-Gomes M, Semin I, Guerra GM, Momsen Reincke S, Sánchez-Sendin E, Yilmaz S, Sempert T, Heinz GA, Tizian C, Raftery M, Schönrich G, Matyushkina D, Smirnov IV, Govorun VM, Schrezenmeier E, Stefanski AL, Dörner T, Zocche S, Viviano E, Klement N, Sehmsdorf KJ, Lunin A, Chang HD, Drutskaya M, Kozlovskaya L, Treskatsch S, Radbruch A, Diefenbach A, Prüss H, Enghard P, Mashreghi MF, Kruglov AA

Link to Pubmed [PMID] – 37944493

Link to DOI – 10.1016/j.chom.2023.10.007

Cell Host Microbe 2023 Nov; 31(11): 1866-1881.e10

The commensal microflora provides a repertoire of antigens that illicit mucosal antibodies. In some cases, these antibodies can cross-react with host proteins, inducing autoimmunity, or with other microbial antigens. We demonstrate that the oral microbiota can induce salivary anti-SARS-CoV-2 Spike IgG antibodies via molecular mimicry. Anti-Spike IgG antibodies in the saliva correlated with enhanced abundance of Streptococcus salivarius 1 month after anti-SARS-CoV-2 vaccination. Several human commensal bacteria, including S. salivarius, were recognized by SARS-CoV-2-neutralizing monoclonal antibodies and induced cross-reactive anti-Spike antibodies in mice, facilitating SARS-CoV-2 clearance. A specific S. salivarius protein, RSSL-01370, contains regions with homology to the Spike receptor-binding domain, and immunization of mice with RSSL-01370 elicited anti-Spike IgG antibodies in the serum. Additionally, oral S. salivarius supplementation enhanced salivary anti-Spike antibodies in vaccinated individuals. Altogether, these data show that distinct species of the human microbiota can express molecular mimics of SARS-CoV-2 Spike protein, potentially enhancing protective immunity.