Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan;61(2):299-312.
doi: 10.1111/apt.18349. Epub 2024 Oct 29.

XBB.1.5-Adapted COVID-19 mRNA Vaccines but Not Infections With Previous Omicron Variants Boost Neutralisation Against the SARS-CoV-2 JN.1 Variant in Patients With Inflammatory Bowel Disease

Simon Woelfel  1   2 , Joel Dütschler  1   3 , Daniel Junker  4 , Marius König  1 , Nicole Graf  5 , Claudia Krieger  1 , Samuel Truniger  1   3 , Vasileios Oikonomou  6 , Georg Leinenkugel  7 , Seraina Koller  1 , Katline Metzger-Peter  7 , Jacqueline Wyss  6 , Niklas Krupka  6 , Nicola Frei  1 ; STAR SIGN Study Investigators; Werner C Albrich  8 , Matthias Friedrich  9 , Jan Hendrik Niess  7   10 , Nicole Schneiderhan-Marra  4 , Alex Dulovic  4 , Benjamin Misselwitz  6   11 , Wolfgang Korte  12 , Justus J Bürgi  12 , Stephan Brand  1
Affiliations

XBB.1.5-Adapted COVID-19 mRNA Vaccines but Not Infections With Previous Omicron Variants Boost Neutralisation Against the SARS-CoV-2 JN.1 Variant in Patients With Inflammatory Bowel Disease

Simon Woelfel et al. Aliment Pharmacol Ther. 2025 Jan.

Abstract

Background: Variant-adapted COVID-19 vaccines are recommended for patients with inflammatory bowel disease (IBD). However, many patients rely on pre-existing immunity by original vaccines or prior infections.

Aim: To assess whether such immunity sufficiently combats the highly immune-evasive SARS-CoV-2 JN.1 variant.

Methods: Utilising two longitudinal cohorts, we evaluated immunity against JN.1 induced by original vaccines (IBD: n = 98; healthy: n = 48), omicron breakthrough infection (IBD: n = 55; healthy: n = 57) or XBB.1.5-adapted vaccines (IBD: n = 18). Neutralisation and anti-receptor-binding domain (RBD) IgG levels against wild-type SARS-CoV-2 and JN.1 were assessed using multiplex immunoassays. Study outcomes were wild-type and JN.1 neutralisation following three doses of original mRNA vaccines, stratified by immunosuppressive therapy (primary outcome), and JN.1 neutralisation following third-dose breakthrough infection or a fourth dose of XBB.1.5-adapted mRNA vaccines (secondary outcomes).

Results: Following original vaccines, JN.1 neutralisation was lower than wild-type neutralisation in all study groups (healthy, anti-TNF and non-anti-TNF; each p < 0.001); most individuals lacked JN.1 neutralisation (healthy: 97.9%; anti-TNF: 98.3% and non-anti-TNF: 92.3%). Confounder-adjusted multivariable modelling strongly associated anti-TNF therapy with low levels of anti-JN.1-RBD IgG (fold-change 0.48 [95% CI 0.39-0.59]). JN.1 neutralisation was similar in patients with or without breakthrough infection (anti-TNF, non-anti-TNF; each p > 0.05); neutralisation failure was 100% despite breakthrough infection. XBB.1.5-adapted vaccines enhanced JN.1 neutralisation (p < 0.001) and reduced neutralisation failure rates in patients with IBD (94.4% pre-vaccination vs. 44.4% post-vaccination; p = 0.003).

Conclusions: Only variant-adapted vaccines protect against emerging SARS-CoV-2 variants. Patients with IBD and healthy individuals without recent vaccination may lack protection against the JN.1 subvariant KP.3 which causes current COVID-19 surges.

Keywords: COVID‐19; Crohn's disease; SARS‐CoV‐2; adapted COVID‐19 vaccines; anti‐TNF therapy; biologics; inflammatory bowel disease; infliximab; mRNA vaccines; ulcerative colitis.

PubMed Disclaimer

References

    1. D. Y. Lin, Y. Du, Y. Xu, et al., “Durability of XBB.1.5 Vaccines Against Omicron Subvariants,” New England Journal of Medicine 390, no. 22 (2024): 2124–2127.
    1. Y. Xie, T. Choi, and A.‐A. Ziyad, “Postacute Sequelae of SARS‐CoV‐2 Infection in the Pre‐Delta, Delta, and Omicron Eras,” New England Journal of Medicine 391, no. 6 (2024): 515–525.
    1. A. M. Carabelli, T. P. Peacock, L. G. Thorne, W. T. Harvey, and J. Hughes, “COVID‐19 Genomics UK Consortium, Et al. SARS‐CoV‐2 Variant Biology: Immune Escape, Transmission and Fitness,” Nature Reviews. Microbiology 21, no. 3 (2023): 162–177.
    1. L. Premkumar, B. Segovia‐Chumbez, R. Jadi, et al., “The Receptor‐Binding Domain of the Viral Spike Protein Is an Immunodominant and Highly Specific Target of Antibodies in SARS‐CoV‐2 Patients,” Science Immunology 5, no. 48 (2020): eabc8413.
    1. S. Yang, Y. Yu, Y. Xu, et al., “Fast Evolution of SARS‐CoV‐2 BA.2.86 to JN.1 Under Heavy Immune Pressure,” Lancet Infectious Diseases 24, no. 2 (2024): e70–e72.

MeSH terms

Supplementary concepts

LinkOut - more resources