Third and Fourth Vaccine Doses Broaden and Prolong Immunity to SARS-CoV-2 in Adult Patients with Immune-Mediated Inflammatory Diseases

Pillar 4
Functional Genomics & Structure-Function of VOCs

We previously demonstrated that immune responses in patients with immune-mediated inflammatory diseases (IMID) waned more rapidly after a 2^nd dose of SARS-CoV-2 mRNA vaccination compared to healthy controls.  This prompted prioritizing 3^rd doses in patients with IMID. In our second study in this series, we examined the effects of 3^rd doses on immune responses at 2-4 weeks following 3rd vaccination and saw that the decreased T-cell stimulation that occurs after 2^nd doses was restored overall following a 3^rd dose of vaccine, and robust antibody and T-cell responses to Omicron and ancestral strains of virus were sustained in patients with IMID.

Following on these studies, we next looked at immune responses in patients with IMID by measuring antibody levels, antibody binding and recognition, and T-cell responses at 3-4 months after 3^rd and 4^th doses of SARS-CoV-2 vaccine by measuring responses against wild-type, Ba.1, and BA.5 variants. We found that third doses were sufficient to restore and prolong antibody and T-cell responses in IMID patients at longer timepoints following vaccination. Additionally, antibody recognition and binding against several variants was broadened, suggesting a larger breadth in antibody response. The effects of 4^th doses were minimal but also prolonged.  Interestingly, patients treated with anti-TNF, especially those treated for Inflammatory bowel disease, showed lower antibody responses, even after 4^th doses.  T-cell responses increased with successive doses where early production of cytokines was predictive of neutralization responses at prolonged timepoints. Our study supports the recommendation for three- and four-dose vaccination regimens in IMID patients.

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