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

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.

Impaired Humoral Immunity with Concomitant Preserved T Cell Reactivity in IBD Patients on Treatment with Infliximab 6 Month after Vaccination with the SARS-CoV-2 mRNA Vaccine BNT162b2: A Pilot Study

“…In contrast, patients treated with vedolizumab were unaffected in their humoral immunity compared to healthy controls, which can be explained by the mechanism of action in targeting a gut-specific anti-integrin that does not impair systemic immunity and is in line with previous findings [ 42 ]. Furthermore, our results confirm previous studies showing attenuated vaccine efficacy in IBD patients on immunosuppressive therapies after vaccination against various other pathogens.…”

“…In the study recently published by Li et al, robust T-cell reactivity was demonstrated in IBD patients on anti-TNF therapy 8 weeks after vaccination [ 48 ]. According to X et al, T-cellular reactivity was detected in approximately 80% of IBD patients receiving therapy with anti-TNF or vedolizumab at 8 to 10 weeks after COVID-19 secondary inoculation [ 42 ]. Our study was now the first to demonstrate comparable T-cell reactivity in IBD patients on immunosuppressive therapy and healthy individuals even 6 months after second SARS-CoV-2 vaccination.…”

Recent advances in clinical practice: management of inflammatory bowel disease during the COVID-19 pandemic

“…Multiple studies have reported high seroconversion rates following two doses of either the mRNA (BNT162b2, mRNA-1273) or adenoviral vector (ChAdOx1 nCoV-19) vaccines, ranging from 81% to 100% in patients with IBD on immunosuppressive therapy (figure 3). 143–146 In one recent meta-analysis of over 9000 patients with IBD, the pooled seroconversion rate was 0.96 (95% CI 0.94 to 0.97) 147. Of 31 studies included, seroconversion rates were determined over a range of 28–179 days following a second dose of SARS-CoV-2 vaccine.…”

“…Shaded red boxes represent IBD medications with attenuated vaccine response. Figure created based on data from refs 137 143–146 154 175. using BioRender.com.…”

“…CORALE-IBD found a poor correlation between anti-S RBD antibody concentration and T cell clonal response to SARS-CoV-2 vaccines from 303 patients with IBD who were on a range of therapies, although they found that patients with IBD treated with anti-TNF therapy had an augmented T cell clonal depth compared with patients receiving no treatment 152. The CLARITY IBD study, a UK-wide prospective cohort study of patients with IBD investigating the impact of infliximab and vedolizumab, and/or concomitant immunomodulators, on SARS-CoV-2 acquisition, illness and immunity in patients with IBD, reported an uncoupling of anti-S RBD antibodies and anti-spike T cell responses, however, similar T cell responses were observed between infliximab-treated compared with vedolizumab-treated patients after one or two doses of either vaccine 146. Further studies are required to confirm these findings, and to determine the relative contributions of T cell vaccine responses to SARS-CoV-2 immunity in patient with IBD.…”