Publication date: Jul 16, 2025

Mucosal immunity plays a pivotal role in preventing infections with SARS-CoV-2. While COVID-19 mRNA vaccines induce robust systemic immune responses in patients with inflammatory bowel disease (IBD), little is known about their efficacy in the mucosal immune compartment. In this sub-investigation of the ongoing STAR-SIGN study, we present the first analysis of mucosal immunity elicited by XBB. 1.5 mRNA vaccines in immunocompromised patients with IBD. IgG and IgA antibodies targeting the receptor-binding domain of the SARS-CoV-2 JN. 1 variant were quantified longitudinally in the saliva of IBD patients using the multiplex immunoassay MultiCoV-Ab. Antibody levels were quantified before and 2-4 weeks after vaccination with XBB. 1.5 mRNA vaccines. All patients previously received three doses with original COVID-19 vaccines. Mucosal IgG antibodies were readily induced by XBB. 1.5 mRNA vaccines (p = 0. 0013 comparing pre- and post-vaccination levels). However, mucosal IgA levels were comparable before and after vaccination (p = 0. 8233). Consequently, mucosal IgG and IgA antibody levels correlated only moderately before and after immunization (pre-vaccination: r = 0. 5294; p = 0. 0239; post-vaccination: r = 0. 4863; p = 0. 0407). Contrary to a previous report in healthy individuals, vaccination did not induce serum IgA in patients with IBD (p = 0. 5841 comparing pre- and post-vaccination levels). These data suggest that COVID-19 mRNA vaccines fail to elicit mucosal IgA in patients with IBD. Since mucosal IgA plays a pivotal role in infection control, the lack of IgA induction indicates that patients lack sufficient protection against SARS-CoV-2 infections which warrants the development of mucosal COVID-19 vaccines.

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