# XBB.1.5 COVID-19 mRNA Vaccines Induce Inadequate Mucosal Immunity in Patients with Inflammatory Bowel Disease

## TL;DR

XBB.1.5 mRNA vaccines do not effectively boost mucosal IgA immunity in inflammatory bowel disease patients, leaving them vulnerable to SARS-CoV-2 infections.

## Contribution

First analysis of mucosal immunity elicited by XBB.1.5 mRNA vaccines in immunocompromised IBD patients.

## Key findings

- XBB.1.5 mRNA vaccines induce mucosal IgG antibodies but not IgA in IBD patients.
- Mucosal IgG and IgA levels correlate only moderately before and after vaccination.
- Vaccination does not increase serum IgA in IBD patients, unlike in healthy individuals.

## Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.