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

• Published in: Nature communications Vol. 13; no. 1; pp. 1379 - 14
• Main Authors: Lin, Simeng, Kennedy, Nicholas A., Saifuddin, Aamir, Sandoval, Diana Muñoz, Reynolds, Catherine J., Seoane, Rocio Castro, 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, Ailsa L., Irving, Peter M., Jones, Gareth-Rhys, Kok, Klaartje B., Lamb, Christopher A., Lees, Charlie W., Altmann, Daniel M., Boyton, Rosemary J., Goodhand, James R., Powell, Nick, Ahmad, Tariq
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/2152/2153; 631/250/590; 631/326/596/4130; 692/4020/1503/257; Antibodies; Antibodies, Monoclonal, Humanized - therapeutic use; BNT162 Vaccine; ChAdOx1 nCoV-19; COVID-19; COVID-19 Vaccines; Health risks; Humanities and Social Sciences; Humans; Immunity; Immunity (Disease); Immunosuppressive agents; Infections; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Infliximab; Infliximab - therapeutic use; Influenza; Intestine; Lymphocytes; Lymphocytes T; Monoclonal antibodies; multidisciplinary; Patients; Public health; Risk; SARS-CoV-2; Schedules; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; T-Lymphocytes; TNF inhibitors; Tumor Necrosis Factor Inhibitors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; Vaccination; Vaccines; Viral diseases; Viral Vaccines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28517-z

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. Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.