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

, Simeng Lin, Nicholas A. Kennedy, Aamir Saifuddin, Diana Muñoz Sandoval, Catherine J. Reynolds, Rocio Castro Seoane, Sherine H. Kottoor, Franziska P. Pieper, Kai Min Lin, David K. Butler, Neil Chanchlani, Rachel Nice, Desmond Chee, Claire Bewshea, Malik Janjua, Timothy J. McDonald, Shaji Sebastian, James L. Alexander, Laura ConstableJames C. Lee, Charles D. Murray, Ailsa L. Hart, Peter M. Irving, Gareth Rhys Jones, Klaartje B. Kok, Christopher A. Lamb, Charlie W. Lees, Daniel M. Altmann, Rosemary J. Boyton, James R. Goodhand, Nick Powell, Tariq Ahmad, Klaartje B. Kok, Farjhana Bokth, Bessie Cipriano, Caroline Francia, Nosheen Khalid, Hafiza Khatun, Ashley Kingston, Irish Lee, Anouk Lehmann, Kinnari Naik, Elise Pabriaga, Nicolene Plaatjies, Kevin Samuels, Rebecca Saich, Hayley Cousins, Wendy Fraser, Rachel Thomas, Craig Mowat

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54 Citations (Scopus)
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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.

Original languageEnglish
Article number1379
Number of pages14
JournalNature Communications
Volume13
Issue number1
Early online date16 Mar 2022
DOIs
Publication statusPublished - Dec 2022

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General
  • General Physics and Astronomy

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