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 language | English |
|---|---|
| Article number | 1379 |
| Number of pages | 14 |
| Journal | Nature Communications |
| Volume | 13 |
| Issue number | 1 |
| Early online date | 16 Mar 2022 |
| DOIs | |
| Publication status | Published - Dec 2022 |
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry,Genetics and Molecular Biology
- General
- General Physics and Astronomy
Fingerprint
Dive into the research topics of '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'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: Nature Communications, Vol. 13, No. 1, 1379, 12.2022.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - 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
AU - Lin, Simeng
AU - Kennedy, Nicholas A.
AU - Saifuddin, Aamir
AU - Sandoval, Diana Muñoz
AU - Reynolds, Catherine J.
AU - Seoane, Rocio Castro
AU - Kottoor, Sherine H.
AU - Pieper, Franziska P.
AU - Lin, Kai Min
AU - Butler, David K.
AU - Chanchlani, Neil
AU - Nice, Rachel
AU - Chee, Desmond
AU - Bewshea, Claire
AU - Janjua, Malik
AU - McDonald, Timothy J.
AU - Sebastian, Shaji
AU - Alexander, James L.
AU - Constable, Laura
AU - Lee, James C.
AU - Murray, Charles D.
AU - Hart, Ailsa L.
AU - Irving, Peter M.
AU - Jones, Gareth Rhys
AU - Kok, Klaartje B.
AU - Lamb, Christopher A.
AU - Lees, Charlie W.
AU - Altmann, Daniel M.
AU - Boyton, Rosemary J.
AU - Goodhand, James R.
AU - Powell, Nick
AU - Ahmad, Tariq
AU - CLARITY IBD study
AU - Kok, Klaartje B.
AU - Bokth, Farjhana
AU - Cipriano, Bessie
AU - Francia, Caroline
AU - Khalid, Nosheen
AU - Khatun, Hafiza
AU - Kingston, Ashley
AU - Lee, Irish
AU - Lehmann, Anouk
AU - Naik, Kinnari
AU - Pabriaga, Elise
AU - Plaatjies, Nicolene
AU - Samuels, Kevin
AU - Saich, Rebecca
AU - Cousins, Hayley
AU - Fraser, Wendy
AU - Thomas, Rachel
AU - Mowat, Craig
N1 - Funding Information: CLARITY IBD is an investigator-led, UK National Institute for Health Research COVID-19 urgent public health study, funded by the Royal Devon and Exeter NHS Foundation Trust, NIHR Imperial Biomedical Research Centre, Hull University Teaching Hospital NHS Trust, UKRI (MR/V036939/1) and by unrestricted educational grants from F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea), Takeda (UK) and Galapagos NV (Belgium). None of our funding bodies had any role in study design, data collection or analysis, writing, or decision to submit for publication. The NIHR Clinical Research Network supported study set-up, site identification and delivery of this study. This was facilitated by Professor Mark Hull, the National Speciality Lead for Gastroenterology. We acknowledge the contribution of our Patient Advisory Group who helped shape the trial design around patient priorities. Our partners, Crohn’s and Colitis UK (CCUK), continue to support this group and participate in Study Management Team meetings. We thank Professor Graham Cooke and Dr Katrina Pollock for their helpful discussions and review of the data. Laboratory tests were undertaken by the Exeter Blood Sciences Laboratory at the Royal Devon and Exeter NHS Foundation Trust. The Exeter NIHR Clinical Research Facility coordinated sample storage and management. This research used data assets made available by National Safe Haven as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (research which commenced between 1 October 2020–31 March 2021 grant ref MC_PC_20029; 1 April 2021–30 September 2022 grant ref MC_PC_20058). Tariq Malik and James Thomas from Public Health England, Guy Stevens, Katie Donelon, Elen de Lacy from Public Health Wales and Johanna Bruce from Public Health Scotland supported linkage of central SARS-CoV-2 PCR test results with study data. Roche Diagnostics Limited provided the Elecsys Anti-SARS-CoV-2 immunoassay for the study. 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 and The Queen’s Medical Research Institute at the University of Edinburgh facilitated PBMC extractions for the T cell experiments. We thank Professor Robert Aldridge for access to data from the Virus Watch Collaborative. S.L. is supported by a Wellcome GW4-CAT fellowship (222850/Z/21/Z). N.C. acknowledges support from CCUK. J.C.L. is a Lister Prize Fellow and acknowledges support from the Cambridge NIHR Biomedical Research Centre and the Francis Crick Institute which receives core funding from Cancer Research UK (FC001169), the UK Medical Research Council (FC001169) and the Wellcome Trust (FC001169). G.-R.J. is supported by a Wellcome Trust Clinical Research Career Development Fellowship (220725/Z/20/Z). C.A.L. acknowledges support from the NIHR Newcastle Biomedical Research Centre and the support of the Programmed Investigation Unit at Royal Victoria Infirmary, Newcastle upon Tyne. C.W.L. is funded by a UKRI Future Leaders Fellowship. R.J.B. and D.M.A. are supported by MRC (MR/W020610/1, MR/S019553/1, MR/R02622X/1 and MR/V036939/1), NCSi4P, NIHR EME NIHR134607 and NIHR COV-LT2-0027, Innovate UK SBRI894, NIHR Imperial Biomedical Research Centre (BRC):ITMAT, Cystic Fibrosis Trust SRC (2019SRC015) and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network (ITN) European Training Network (No 860325). N.P. is supported by the NIHR Imperial Biomedical Research Center (BRC). We acknowledge the study co-ordinators of the Exeter Inflammatory Bowel Disease Research Group: Marian Parkinson and Helen Gardner-Thorpe for their ongoing administrative support to the study. The sponsor of the study was the Royal Devon and Exeter NHS Foundation Trust. Funding Information: Dr. S Lin reports non-financial support from Pfizer, non-financial support from Ferring, outside the submitted work. Dr. Kennedy reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study; grants and non-financial support from AbbVie, grants and personal fees from Celltrion, personal fees and non-financial support from Janssen, personal fees from Takeda, personal fees and non-financial support from Dr. Falk, outside the submitted work. Dr. Saifuddin has received travel expense support from Dr. Falk Pharma. Dr. Chee reports non-financial support from Ferring, personal fees and non-financial support from Pfizer, outside the submitted work. Prof. Sebastian reports grants from Takeda, Abbvie, AMGEN, Tillots Pharma, personal fees from Jaansen, Takeda, Galapagos, Celltrion, Falk Pharma, Tillots pharma, Cellgene, Pfizer, Pharmacocosmos, outside the submitted work. Dr. Alexander reports sponsorship from Vifor Pharma for accommodation/travel to BSG 2019, outside the submitted work. Dr. Lee reports personal fees from Abbvie, personal fees from C4X Discovery, personal fees from PredictImmune and personal fees from AG pus diagnostics. Dr. Hart reports personal fees from Abbvie, personal fees from Allergan, personal fees from BMS, personal fees from Celltrion, personal fees from Falk, personal fees from GSK, personal fees from Takeda, personal fees from Pfizer, personal fees from Janssen, personal fees from Galapogos, personal fees from AstraZeneca, outside the submitted work. Dr. Irving reports grants and personal fees from Takeda, grants from MSD, grants and personal fees from Pfizer, personal fees from Galapagos, personal fees from Gilead, personal fees from Abbvie, personal fees from Janssen, personal fees from Boehringer Ingelheim, personal fees from Topivert, personal fees from VH2, personal fees from Celgene, personal fees from Arena, personal fees from Samsung Bioepis, personal fees from Sandoz, personal fees from Procise, personal fees from Prometheus, outside the submitted work. Dr. Jones has received speaker fees from Takeda, Ferring and Janssen. Dr. Kok reports personal fees from Janssen, personal fees from Takeda, personal fees from PredictImmune, personal fees from Amgen, outside the submitted work. Dr. Lamb reports grants from Genentech, grants and personal fees from Janssen, grants and personal fees from Takeda, grants from AbbVie, personal fees from Ferring, grants from Eli Lilly, grants from Pfizer, grants from Roche, grants from UCB Biopharma, grants from Sanofi Aventis, grants from Biogen IDEC, grants from Orion OYJ, personal fees from Dr. Falk Pharma, grants from Astra Zeneca, outside the submitted work. Prof. Lees reports personal fees from Abbvie, personal fees from Janssen, personal fees from Pfizer, personal fees from Takeda, grants from Gilead, personal fees from Gilead, personal fees from Galapagos, personal fees from Iterative Scopes, personal fees from Trellus Health, personal fees from Celltion, personal fees from Ferring, personal fees from BMS, during the conduct of the study. Prof Boyton and Prof Altmann are members of the Global T cell Expert Consortium and have consulted for Oxford Immunotec outside the submitted work. Dr. Goodhand reports grants from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study. Dr. Powell reports personal fees from Takeda, personal fees from Janssen, personal fees from Pfizer, personal fees from Bristol-Myers Squibb, personal fees from Abbvie, personal fees from Roche, personal fees from Lilly, personal fees from Allergan, personal fees from Celgene, outside the submitted work; and Dr. Powell has served as a speaker/advisory board member for Abbvie, Allergan, Bristol-Myers Squibb, Celgene, Falk, Ferring, Janssen, Pfizer, Tillotts, Takeda and Vifor Pharma. Prof. Ahmad reports grants and non-financial support from F. Hoffmann-La Roche AG, grants from Biogen Inc, grants from Celltrion Healthcare, grants from Galapagos NV, non-financial support from Immundiagnostik, during the conduct of the study; personal fees from Biogen inc, grants and personal fees from Celltrion Healthcare, personal fees and non-financial support from Immundiagnostik, personal fees from Takeda, personal fees from ARENA, personal fees from Gilead, personal fees from Adcock Ingram Healthcare, personal fees from Pfizer, personal fees from Genentech, non-financial support from Tillotts, outside the submitted work. The following authors have nothing to declare: Diana Muñoz Sandoval, Catherine Reynolds, Rocio Castro Seoane, Sherine H Kottoor, Franziska Pieper, Kai-Min Lin, David Butler, Neil Chanchlani, Claire Bewshea, Rachel Nice, Laura Constable, Charles D Murray, Timothy J McDonald. Funding Information: CLARITY IBD is an investigator-led, UK National Institute for Health Research COVID-19 urgent public health study, funded by the Royal Devon and Exeter NHS Foundation Trust, NIHR Imperial Biomedical Research Centre, Hull University Teaching Hospital NHS Trust, UKRI (MR/V036939/1) and by unrestricted educational grants from F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea), Takeda (UK) and Galapagos NV (Belgium). None of our funding bodies had any role in study design, data collection or analysis, writing, or decision to submit for publication. The NIHR Clinical Research Network supported study set-up, site identification and delivery of this study. This was facilitated by Professor Mark Hull, the National Speciality Lead for Gastroenterology. We acknowledge the contribution of our Patient Advisory Group who helped shape the trial design around patient priorities. Our partners, Crohn’s and Colitis UK (CCUK), continue to support this group and participate in Study Management Team meetings. We thank Professor Graham Cooke and Dr Katrina Pollock for their helpful discussions and review of the data. Laboratory tests were undertaken by the Exeter Blood Sciences Laboratory at the Royal Devon and Exeter NHS Foundation Trust. The Exeter NIHR Clinical Research Facility coordinated sample storage and management. This research used data assets made available by National Safe Haven as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (research which commenced between 1 October 2020–31 March 2021 grant ref MC_PC_20029; 1 April 2021–30 September 2022 grant ref MC_PC_20058). Tariq Malik and James Thomas from Public Health England, Guy Stevens, Katie Donelon, Elen de Lacy from Public Health Wales and Johanna Bruce from Public Health Scotland supported linkage of central SARS-CoV-2 PCR test results with study data. Roche Diagnostics Limited provided the Elecsys Anti-SARS-CoV-2 immunoassay for the study. 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 and The Queen’s Medical Research Institute at the University of Edinburgh facilitated PBMC extractions for the T cell experiments. We thank Professor Robert Aldridge for access to data from the Virus Watch Collaborative. S.L. is supported by a Wellcome GW4-CAT fellowship (222850/Z/21/Z). N.C. acknowledges support from CCUK. J.C.L. is a Lister Prize Fellow and acknowledges support from the Cambridge NIHR Biomedical Research Centre and the Francis Crick Institute which receives core funding from Cancer Research UK (FC001169), the UK Medical Research Council (FC001169) and the Wellcome Trust (FC001169). G.-R.J. is supported by a Wellcome Trust Clinical Research Career Development Fellowship (220725/Z/20/Z). C.A.L. acknowledges support from the NIHR Newcastle Biomedical Research Centre and the support of the Programmed Investigation Unit at Royal Victoria Infirmary, Newcastle upon Tyne. C.W.L. is funded by a UKRI Future Leaders Fellowship. R.J.B. and D.M.A. are supported by MRC (MR/W020610/1, MR/S019553/1, MR/R02622X/1 and MR/V036939/1), NCSi4P, NIHR EME NIHR134607 and NIHR COV-LT2-0027, Innovate UK SBRI894, NIHR Imperial Biomedical Research Centre (BRC):ITMAT, Cystic Fibrosis Trust SRC (2019SRC015) and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network (ITN) European Training Network (No 860325). N.P. is supported by the NIHR Imperial Biomedical Research Center (BRC). We acknowledge the study co-ordinators of the Exeter Inflammatory Bowel Disease Research Group: Marian Parkinson and Helen Gardner-Thorpe for their ongoing administrative support to the study. The sponsor of the study was the Royal Devon and Exeter NHS Foundation Trust. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85126647052&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-28517-z
DO - 10.1038/s41467-022-28517-z
M3 - Article
C2 - 35296643
AN - SCOPUS:85126647052
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1379
ER -