Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-28517-z
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Funding
- Royal Devon and Exeter NHS Foundation Trust
- NIHR Imperial Biomedical Research Centre, Hull University Teaching Hospital NHS Trust [MR/V036939/1]
- F. Hoffmann-La Roche AG (Switzerland)
- Biogen GmbH (Switzerland)
- Celltrion Healthcare (South Korea)
- Takeda (UK)
- Galapagos NV (Belgium)
- National Speciality Lead for Gastroenterology
- Crohn's and Colitis UK
- Exeter Blood Sciences Laboratory at the Royal Devon and Exeter NHS Foundation Trust - UK Research and Innovation [MC_PC_20029, MC_PC_20058]
- Public Health England
- Elen de Lacy from Public Health Wales
- Public Health Scotland
- Roche Diagnostics Limited
- Faculty of Medicine at Imperial College London, Exeter NIHR Clinical Research Facility, Jeffrey Cheah Biomedical Centre at the University of Cambridge, Newcastle University Medical School
- Wellcome [GW4-CAT, 222850/Z/21/Z]
- Cambridge NIHR Biomedical Research Centre
- Francis Crick Institute
- Cancer Research UK [FC001169]
- UK Medical Research Council [FC001169]
- Wellcome Trust
- Wellcome Trust Clinical Research Career Development Fellowship [220725/Z/20/Z]
- NIHR Newcastle Biomedical Research Centre
- Programmed Investigation Unit at Royal Victoria Infirmary, Newcastle upon Tyne - UKRI Future Leaders Fellowship
- MRC [MR/V036939/1, MR/W020610/1, MR/S019553/1, MR/R02622X/1, NIHR EME NIHR134607, NIHR COV-LT2-0027]
- Innovate UK [SBRI894]
- NIHR Imperial Biomedical Research Centre (BRC):ITMAT
- Cystic Fibrosis Trust SRC [2019SRC015]
- Horizon 2020 Marie Skodowska-Curie Innovative Training Network (ITN) European Training Network [860325]
- NIHR Imperial Biomedical Research Center (BRC)
- Exeter NHS Foundation Trust
- Medical Research Council [MR/W020610/1, MR/V036939/1, MR/R02622X/1, MR/S019553/1] Funding Source: researchfish
- MRC [MR/V036939/1, MR/W020610/1, MR/S019553/1, MR/R02622X/1] Funding Source: UKRI
- Wellcome Trust [220725/Z/20/Z] Funding Source: Wellcome Trust
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This study reports immune responses and breakthrough infections in patients with inflammatory bowel disease receiving anti-TNF treatments after receiving COVID-19 vaccination, and suggests the need for adapted vaccination schedules for these 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. 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.
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