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Robust SARS-CoV-2 antibody and T cell immunity following three COVID-19 vaccine doses in inflammatory bowel disease patients receiving anti-TNF or alternative treatments
  1. Eva Zhang1,2,
  2. Thi H O Nguyen3,
  3. Lilith F Allen3,
  4. Lukasz Kedzierski3,4,
  5. Louise C Rowntree3,
  6. So Young Chang3,
  7. Wuji Zhang3,
  8. Jennifer R Habel3,
  9. Isabelle J Foo3,
  10. Tejas Menon3,
  11. Jeni Mitchell1,
  12. Rupert W Leong2,
  13. Katherine Bond5,6,
  14. Deborah A Williamson6,7,8,
  15. Katherine Kedzierska3,9,
  16. Britt Christensen1,10
  1. 1Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Victoria, Australia
  2. 2Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
  3. 3Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  4. 4Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Melbourne, Victoria, Australia
  5. 5Department of Microbiology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  6. 6Victorian Infectious Disease Reference Laboratory (VIDRL), The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  7. 7Infectious Diseases, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  8. 8Department of Infectious Diseases, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  9. 9Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido, Japan
  10. 10Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
  1. Correspondence to Dr Britt Christensen, Gastroenterology Department, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Britt.Christensen{at}

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We read Kennedy et al1’s findings with interest, and report in-depth analyses of antibody and T cell responses in patients with inflammatory bowel disease (IBD) to COVID-19 vaccination.

We prospectively recruited 100 SARS-CoV-2-uninfected patients with IBD on varying treatments at the Royal Melbourne Hospital (HREC/74403/MH-2021). Healthcare workers who did not have IBD and were not on immunosuppressive medication were enrolled as controls with approvals from Melbourne Health (HREC/68355/MH-2020) and University of Melbourne (HREC 22268, 21626). Participant characteristics are outlined in table 1. IBD medication regimens needed to be stable for at least 8 weeks prior to enrolment. Only one participant was on concomitant low-dose systemic corticosteroids with anti-TNF combination therapy. Eighty-nine patients received BNT162b2 (Pfizer–BioNTech), and 11 received ChAdOx1 nCoV-19 (Oxford–AstraZeneca). No participants had a clinical history of SARS-CoV-2 infection at enrolment.

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Table 1

Characteristics of patients with IBD and healthy controls

Anti-S1/2 and anti-RBD SARS-CoV-2-specific antibodies were measured at baseline and at five time points after COVID-19 vaccination (figure 1A). Whole blood analyses of antibody-secreting cells (ASCs), circulating T follicular helper (Tfh) cells, CD4+ T cells and CD8+ T cells, was performed across V0-V6 to determine activation profiles. Spike protein S1/2 receptor binding domain specific IgG antibodies were measured using the LIAISON DiaSorin electrochemiluminenscence immunoassay. IgG ELISA was used to assess the presence of antibodies against ancestral SARS-CoV-2 RBD in plasma, as previously described.2 Activation-induced marker assay was performed on PBMCs at V0, V3 and V6 time points according to Grifoni et al with minor modifications.3 Four IBD participants were infected with COVID-19 during the study period, which was noted via …

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  • KK and BC are joint senior authors.

  • Twitter @rupertleong, @IBDmedicaldoc

  • EZ and THON contributed equally.

  • Correction notice This article has been corrected since it published Online First. The author's name, Katherine Kedzierska, has been amended.

  • Contributors BC, KK and RWL supervised the study. EZ, THON, LFA, LK, KB, DAW, BC and KK designed the experiments. THON, LFA, LK and LCR performed humoral and T cell experiments. THON, LFA, LCR, SYC, WZ, JRH and IJF processed bloods and performed whole blood staining. EZ, THON, LFA, LK, TM and KB analysed data. EZ, JM and BC recruited the IBD vaccinated patients and collated patients’ clinical data. LCR, JM, KB and DAW recruited the healthy vaccinated cohorts. EZ, THON, LFA, BC and KK wrote the manuscript. All authors reviewed and approved the manuscript.

  • Funding This work was supported by the GESA Rose Amarant Grant to EZ, Eric Charles Smith Grant to BC, NHMRC Leadership Investigator Grant to KK (#1173871), NHMRC Emerging Leadership Level 1 Investigator Grant to THON (#1194036), NHMRC Emerging Leadership Level 2 Investigator Grant to DAW (#1174555), Research Grants Council of the Hong Kong Special Administrative Region, China (#T11-712/19-N n) to KK, MRFF Award (#2016062) to KK, THON and LCR, MRFF Award (#1202445) to KK, MRFF Award (#2005544) to KK.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.