Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab

Lin, Simeng; Kennedy, Nicholas A.; Saifuddin, Aamir; Sandoval, Diana Muñoz; Reynolds, Catherine J.; Castro Seoane, Rocio; Kottoor, Sherine H.; Pieper, Franziska P.; Lin, Kai-Min; Butler, David K.; Chanchlani, Neil; Nice, Rachel; Chee, Desmond; Bewshea, Claire; Janjua, Malik; Mcdonald, Timothy J.; Sebastian, Shaji; Alexander, James L.; Constable, Laura; Lee, James C.; Murray, Charles D.; Hart, Alisa L.; Irving, Peter M.; Jones, Gareth-Rhys

Abstract

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2-27.5] vs 47.6 days [45.5-49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9-36.8] vs 58.0 days [55.0-61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.

Citation

Lin, S., Kennedy, N. A., Saifuddin, A., Sandoval, D. M., Reynolds, C. J., Castro Seoane, R., …Jones, G. (2022). Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab. Nature Communications, 13, Article 1379. https://doi.org/10.1038/s41467-022-28517-z

• Journal Article Type: Article
• Acceptance Date: Jan 26, 2022
• Online Publication Date: Mar 16, 2022
• Publication Date: Mar 16, 2022
• Deposit Date: Oct 30, 2023
• Publicly Available Date: Nov 10, 2023
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Article Number: 1379
• DOI: https://doi.org/10.1038/s41467-022-28517-z
• Public URL: https://nottingham-repository.worktribe.com/output/26797230
• Publisher URL: https://www.nature.com/articles/s41467-022-28517-z