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

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-inve...

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Main Authors: Simon Woelfel, Joel Dütschler, Daniel Junker, Marius König, Georg Leinenkugel, Claudia Krieger, Samuel Truniger, Annett Franke, Seraina Koller, Katline Metzger-Peter, Nicola Frei, STAR SIGN Study Investigators, Werner C. Albrich, Matthias Friedrich, Jan Hendrik Niess, Nicole Schneiderhan-Marra, Alex Dulovic, Wolfgang Korte, Justus J. Bürgi, Stephan Brand
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/7/759
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author Simon Woelfel
Joel Dütschler
Daniel Junker
Marius König
Georg Leinenkugel
Claudia Krieger
Samuel Truniger
Annett Franke
Seraina Koller
Katline Metzger-Peter
Nicola Frei
STAR SIGN Study Investigators
Werner C. Albrich
Matthias Friedrich
Jan Hendrik Niess
Nicole Schneiderhan-Marra
Alex Dulovic
Wolfgang Korte
Justus J. Bürgi
Stephan Brand
author_facet Simon Woelfel
Joel Dütschler
Daniel Junker
Marius König
Georg Leinenkugel
Claudia Krieger
Samuel Truniger
Annett Franke
Seraina Koller
Katline Metzger-Peter
Nicola Frei
STAR SIGN Study Investigators
Werner C. Albrich
Matthias Friedrich
Jan Hendrik Niess
Nicole Schneiderhan-Marra
Alex Dulovic
Wolfgang Korte
Justus J. Bürgi
Stephan Brand
author_sort Simon Woelfel
collection DOAJ
description 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 (<i>p</i> = 0.0013 comparing pre- and post-vaccination levels). However, mucosal IgA levels were comparable before and after vaccination (<i>p</i> = 0.8233). Consequently, mucosal IgG and IgA antibody levels correlated only moderately before and after immunization (pre-vaccination: <i>r</i> = 0.5294; <i>p</i> = 0.0239; post-vaccination: <i>r</i> = 0.4863; <i>p</i> = 0.0407). Contrary to a previous report in healthy individuals, vaccination did not induce serum IgA in patients with IBD (<i>p</i> = 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.
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spelling doaj-art-3a500036a6054f848253e764f5eb4ca62025-08-20T03:56:49ZengMDPI AGVaccines2076-393X2025-07-0113775910.3390/vaccines13070759XBB.1.5 COVID-19 mRNA Vaccines Induce Inadequate Mucosal Immunity in Patients with Inflammatory Bowel DiseaseSimon Woelfel0Joel Dütschler1Daniel Junker2Marius König3Georg Leinenkugel4Claudia Krieger5Samuel Truniger6Annett Franke7Seraina Koller8Katline Metzger-Peter9Nicola Frei10STAR SIGN Study InvestigatorsWerner C. Albrich11Matthias Friedrich12Jan Hendrik Niess13Nicole Schneiderhan-Marra14Alex Dulovic15Wolfgang Korte16Justus J. Bürgi17Stephan Brand18Department of Gastroenterology and Hepatology, HOCH, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandDepartment of Gastroenterology and Hepatology, HOCH, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandNMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, GermanyDepartment of Gastroenterology and Hepatology, HOCH, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandDepartment of Gastroenterology and Hepatology, University Digestive Healthcare Center, Clarunis, 4002 Basel, SwitzerlandDepartment of Gastroenterology and Hepatology, HOCH, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandDepartment of Gastroenterology and Hepatology, HOCH, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandDepartment of Gastroenterology and Hepatology, HOCH, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandDepartment of Gastroenterology and Hepatology, HOCH, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandDepartment of Gastroenterology and Hepatology, University Digestive Healthcare Center, Clarunis, 4002 Basel, SwitzerlandDepartment of Gastroenterology and Hepatology, HOCH, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandDivision of Infectious Diseases, Infection Prevention & Travel Medicine, HOCH, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandTranslational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UKDepartment of Gastroenterology and Hepatology, University Digestive Healthcare Center, Clarunis, 4002 Basel, SwitzerlandNMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, GermanyNMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, GermanyCenter for Laboratory Medicine, 9001 St. Gallen, SwitzerlandCenter for Laboratory Medicine, 9001 St. Gallen, SwitzerlandDepartment of Gastroenterology and Hepatology, HOCH, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandBackground: 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 (<i>p</i> = 0.0013 comparing pre- and post-vaccination levels). However, mucosal IgA levels were comparable before and after vaccination (<i>p</i> = 0.8233). Consequently, mucosal IgG and IgA antibody levels correlated only moderately before and after immunization (pre-vaccination: <i>r</i> = 0.5294; <i>p</i> = 0.0239; post-vaccination: <i>r</i> = 0.4863; <i>p</i> = 0.0407). Contrary to a previous report in healthy individuals, vaccination did not induce serum IgA in patients with IBD (<i>p</i> = 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.https://www.mdpi.com/2076-393X/13/7/759mucosal immunityCOVID-19inflammatory bowel diseaseanti-TNFmRNA vaccinesSARS-CoV-2
spellingShingle Simon Woelfel
Joel Dütschler
Daniel Junker
Marius König
Georg Leinenkugel
Claudia Krieger
Samuel Truniger
Annett Franke
Seraina Koller
Katline Metzger-Peter
Nicola Frei
STAR SIGN Study Investigators
Werner C. Albrich
Matthias Friedrich
Jan Hendrik Niess
Nicole Schneiderhan-Marra
Alex Dulovic
Wolfgang Korte
Justus J. Bürgi
Stephan Brand
XBB.1.5 COVID-19 mRNA Vaccines Induce Inadequate Mucosal Immunity in Patients with Inflammatory Bowel Disease
Vaccines
mucosal immunity
COVID-19
inflammatory bowel disease
anti-TNF
mRNA vaccines
SARS-CoV-2
title XBB.1.5 COVID-19 mRNA Vaccines Induce Inadequate Mucosal Immunity in Patients with Inflammatory Bowel Disease
title_full XBB.1.5 COVID-19 mRNA Vaccines Induce Inadequate Mucosal Immunity in Patients with Inflammatory Bowel Disease
title_fullStr XBB.1.5 COVID-19 mRNA Vaccines Induce Inadequate Mucosal Immunity in Patients with Inflammatory Bowel Disease
title_full_unstemmed XBB.1.5 COVID-19 mRNA Vaccines Induce Inadequate Mucosal Immunity in Patients with Inflammatory Bowel Disease
title_short XBB.1.5 COVID-19 mRNA Vaccines Induce Inadequate Mucosal Immunity in Patients with Inflammatory Bowel Disease
title_sort xbb 1 5 covid 19 mrna vaccines induce inadequate mucosal immunity in patients with inflammatory bowel disease
topic mucosal immunity
COVID-19
inflammatory bowel disease
anti-TNF
mRNA vaccines
SARS-CoV-2
url https://www.mdpi.com/2076-393X/13/7/759
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