COVID-19 vaccine-induced antibody and T-cell responses in immunosuppressed patients with inflammatory bowel disease after the third vaccine dose (VIP): a multicentre, prospective, case-control study


COVID-19 vaccine-induced antibody responses are reduced in patients with inflammatory bowel disease (IBD) taking anti-TNF or tofacitinib after two vaccine doses. We sought to assess whether immunosuppressive treatments were associated with reduced antibody and T-cell responses in patients with IBD after a third vaccine dose.


VIP was a multicentre, prospective, case-control study done in nine centres in the UK. We recruited immunosuppressed patients with IBD and non-immunosuppressed healthy individuals. All participants were aged 18 years or older. The healthy control group had no diagnosis of IBD and no current treatment with systemic immunosuppressive therapy for any other indication. The immunosuppressed patients with IBD had an established diagnosis of Crohn's disease, ulcerative colitis, or unclassified IBD using standard definitions of IBD, and were receiving established treatment with one of six immunosuppressive regimens for at least 12 weeks at the time of first dose of SARS-CoV-2 vaccination. All participants had to have received three doses of an approved COVID-19 vaccine. SARS-CoV-2 spike antibody binding and T-cell responses were measured in all participant groups. The primary outcome was anti-SARS-CoV-2 spike (S1 receptor binding domain [RBD]) antibody concentration 28–49 days after the third vaccine dose, adjusted by age, homologous versus heterologous vaccine schedule, and previous SARS-CoV-2 infection. The primary outcome was assessed in all participants with available data.


Between Oct 18, 2021, and March 29, 2022, 352 participants were included in the study (thiopurine n=65, infliximab n=46, thiopurine plus infliximab combination therapy n=49, ustekinumab n=44, vedolizumab n=50, tofacitinib n=26, and healthy controls n=72). Geometric mean anti-SARS-CoV-2 S1 RBD antibody concentrations increased in all groups following a third vaccine dose, but were significantly lower in patients treated with infliximab (2736·8 U/mL [geometric SD 4·3]; p<0·0001), infliximab plus thiopurine (1818·3 U/mL [6·7]; p<0·0001), and tofacitinib (8071·5 U/mL [3·1]; p=0·0018) compared with the healthy control group (16 774·2 U/mL [2·6]). There were no significant differences in anti-SARS-CoV-2 S1 RBD antibody concentrations between the healthy control group and patients treated with thiopurine (12 019·7 U/mL [2·2]; p=0·099), ustekinumab (11 089·3 U/mL [2·8]; p=0·060), or vedolizumab (13 564·9 U/mL [2·4]; p=0·27). In multivariable modelling, lower anti-SARS-CoV-2 S1 RBD antibody concentrations were independently associated with infliximab (geometric mean ratio 0·15 [95% CI 0·11–0·21]; p<0·0001), tofacitinib (0·52 [CI 0·31–0·87]; p=0·012), and thiopurine (0·69 [0·51–0·95]; p=0·021), but not with ustekinumab (0·64 [0·39–1·06]; p=0·083), or vedolizumab (0·84 [0·54–1·30]; p=0·43). Previous SARS-CoV-2 infection (1·58 [1·22–2·05]; p=0·0006) was independently associated with higher anti-SARS-CoV-2 S1 RBD antibody concentrations and older age (0·88 [0·80–0·97]; p=0·0073) was independently associated with lower anti-SARS-CoV-2 S1 RBD antibody concentrations. Antigen-specific T-cell responses were similar in all groups, except for recipients of tofacitinib without evidence of previous infection, where T-cell responses were significantly reduced relative to healthy controls (p=0·021).


A third dose of COVID-19 vaccine induced a boost in antibody binding in immunosuppressed patients with IBD, but these responses were reduced in patients taking infliximab, infliximab plus thiopurine, and tofacitinib. Tofacitinib was also associated with reduced T-cell responses. These findings support continued prioritisation of immunosuppressed groups for further vaccine booster dosing, particularly patients on anti-TNF and JAK inhibitors.

Author list



  1. Department of Metabolism, Digestion and Reproduction 
  2. Department of Infectious Disease 
  3. Department of Surgery and Cancer and Department of Immunology and Inflammation, Imperial College London, London, UK;
  4. Department of Gastroenterology and Division of Medicine and Integrated Care, Imperial College Healthcare NHS Trust, London, UK;
  5. Department of Gastroenterology, St Mark’s Hospital and Academic Institute, London, UK 
  6. Exeter Inflammatory Bowel Disease and Pharmacogenetics Research Group, University of Exeter, Exeter, UK
  7. Department of Clinical Chemistry, Biochemistry, Exeter Clinical Laboratory International and Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK;
  8. Department of Gastroenterology, Western General Hospital, NHS Lothian, Edinburgh, UK
  9. Centre for Inflammation Research, The Queen’s Medical Research Institute,The University of Edinburgh, Edinburgh, UK 
  10. Nightingale-Saunders Clinical Trials and Epidemiology Unit, King’s Clinical Trials Unit and School of Immunology and Microbial Sciences, King’s College London, London, UK;
  11. Department of Gastroenterology, Hull University Teaching Hospitals NHS Trust, Hull, UK 
  12. Hull York Medical School, University of Hull, Hull, UK 
  13. Department of Gastroenterology and Lung Division, Royal Brompton and Harefield Hospitals, Guy’s and St Thomas’ NHS Foundation Trust, London, UK;
  14. Department of Gastroenterology, King’s College Hospital, London, UK 
  15. The NIHR Bioresource, University of Cambridge, Cambridge, UK 
  16. Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, UK 
  17. Department of Gastroenterology, Bart’s Health NHS Trust, London, UK 
  18. Department of Gastroenterology, St George’s Hospital NHS Trust, London, UK



James L Alexander*, Zhigang Liu*, Diana Muñoz Sandoval*, Catherine Reynolds*, Hajir Ibraheim, Sulak Anandabaskaran, Aamir Saifuddin, Rocio Castro Seoane, Nikhil Anand, Rachel Nice, Claire Bewshea, Andrea D’Mello, Laura Constable, Gareth R Jones, Sharmili Balarajah, Francesca Fiorentino, Shaji Sebastian, Peter M Irving, Lucy C Hicks, Horace R T Williams, Alexandra J Kent, Rachel Linger, Miles Parkes, Klaartje Kok, Kamal V Patel, Julian P Teare, Daniel M Altmann, James R Goodhand, Ailsa L Hart, Charlie W Lees, Rosemary J Boyton*, Nicholas A Kennedy*, Tariq Ahmad*, Nick Powell* on behalf of the VIP study investigators†

Novel Coronavirus SARS-CoV-2


The Lancet - Gastroenterology & Hepatology