Higher and Sustained Cell-Mediated Immune Responses after Three Doses of mRNA COVID-19 Vaccine In Patients with Inflammatory Bowel Disease on Anti-TNF Therapy.

INTRODUCTION: Studies suggest that the generation of durable T cell immunity following COVID-19 vaccination protects against severe disease. The aim of this study was to measure cell mediated immune response (CMIR) one to two months and six months after a third dose of a COVID-19 mRNA vaccine.

METHODS: This prospective study (HERCULES) evaluated CMIR at 28-65 days (t1) after dose 2, 28-65 days (t2) (n=183) and six months (+/-45 days) (t3) (n=167) after a third dose of an mRNA COVID-19 vaccine. A small cohort had blood available 28-65 days (t4) (n=55) after a fourth dose. Primary outcomes were CMIR at (t2) and (t3). Secondary outcomes included the effect of immunosuppressing IBD medications on CMIR and response at (t4).

RESULTS: All patients had measurable CMIR at all time points. CMIR increased at t2 compared to t1 (median 1467 responding cells per million (interquartile range (IQR) 410-5971) vs 313 (94-960) p< 0.001). There was no significant waning when comparing t2 vs t3 or significant boosting at t4. Those on anti-TNF monotherapy had a higher CMIR compared to those not on this therapy at t2 (4132 ( IQR 1136-8795) vs. 869 (IQR 343-3221) p <0.001) and t3 (2843 (IQR 596-6459) vs 654 (IQR 143-2067) p<0.001). In univariable analysis, anti-TNF monotherapy was associated with a higher CMIR at t2 (p< 0.001) and t3 (p< 0.001) and confirmed in a multivariable model (p< 0.001).

CONCLUSION: A third dose of a COVID-19 vaccine boosts CMIR, and the response is sustained in patients with IBD.