BACKGROUND AND AIMS Vaccine-mediated immune responses in patients with inflammatory bowel disease (IBD) may be influenced by IBD therapies. We investigated in-depth humoral and T-cell responses to SARS-CoV-2 vaccination in IBD patients following three COVID-19 vaccine doses.

METHODS Immune responses of 100 SARS-CoV-2-uninfected IBD patients on varying treatments were compared to healthy controls (n=35). Anti-S1/2 and anti-RBD SARS-CoV-2-specific antibodies, CD4+ and CD8+ T-cell responses were measured at baseline and at five time-points after COVID-19 vaccination.

RESULTS Anti-S1/2 and anti-RBD antibody concentrations at ∼1 month after second dose vaccination were significantly lower in anti-TNF-treated patients compared to non-TNF IBD patients and healthy controls (126.4 vs 262.1 and 295.5, p<0.0001). Anti-S1/2 antibodies remained reduced in anti-TNF treated patients before and after the third dose (285.7 vs 365.3, p=0.03), although anti-RBD antibodies reached comparable titres to non-TNF patients. Anti-RBD antibodies were higher in the vedolizumab group than controls after second dose (4.2 vs 3.6, p=0.003). Anti-TNF monotherapy was associated with increased CD4+ and CD8+ T-cell activation compared to combination anti-TNF patients after second dose, but comparable after third dose. Overall, IBD patients demonstrated similar CD4+/CD8+ T-cell responses compared to healthy controls regardless of treatment regimen.

CONCLUSIONS Anti-TNFs impaired antibody concentrations when compared to non-TNF patients and controls after two vaccine doses. These differences were not observed after the third vaccine dose. However, vaccine induced SARS-CoV-2-specific T cell responses are robust in anti-TNF-treated patients. Our study supports the need for timely booster vaccination particularly in anti-TNF treated patients to minimise the risk of severe SARS-CoV-2 infection.

The authors have declared no competing interest.

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) to KK, MRFF Award (#2016062) to KK, THON and LCR, MRFF Award (#1202445) to KK, MRFF Award (#2005544) to KK.

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Melbourne Health (HREC/74403/MH-2021), (HREC/68355/MH-2020) and University of Melbourne (HREC 22268, 21626).

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Competing interests None declared.

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) to KK, MRFF Award (#2016062) to KK, THON and LCR, MRFF Award (#1202445) to KK, MRFF Award (#2005544) to KK.

All data produced in the present study are available upon reasonable request to the authors