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 Mūnoz Sandoval, Catherine J. Reynolds, Rocio Castro Seoane, Sherine Hermangild 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 Constable, James Lee, Charles Murray, Ailsa Hart, Peter M. Irving, Gareth‐Rhys Jones, Klaartje Kok, Christopher A Lamb, Charlie W. Lees, Daniel M. Altmann, Rosemary J. Boyton, James Goodhand, Nick Powell, Tariq Ahmad, CLARITY IBD study, Klaartje Kok, Farjhana Bokth, Bessie Cipriano, C. 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, Matthew A. Brown, Benjamin White, Nikolaos Kirkineziadis, Bernadette Tilley, Rafeeq Muhammed, Rehana Bi, Catherine Cotter, Jayne Grove, Kate Hong, Ruth Howman, Monica J. Mitchell, Sophie Clayton, Sugrah Sultan, Melanie Rooney, Charlotte Cottrill, Salil Singh, Chris Dawe, R. Hull, Nataliê Silva, Jonathan Manning, Lauren Finlayson, Allison Roebuck, Joy Dawson, Sunil Sonwalkar, Naomi Chambers, Matthew Robinson, Andrew Haigh, Lear Matapure, Tim Raine, Varun George, Christina Kapizioni, Konstantina Strongili, Tina L. Thompson, Mohamed Ahmed, Christos K. Kontos, Christophe Bourges, Isabella Barbutti, Megan E. Gozzard, Philip Hendy, Rhian Bull, Patricia Costa, Lisa Davey, Hayley Hannington, Kribashnie Nundlall, Catarina Martins, Laura Avanzi, Jaime Carungcong, Sabrina Barr, Richard Appleby, Emma C. Johnson
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.