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 2nd dose of SARS-CoV-2 mRNA vaccination compared to healthy controls.  This prompted prioritizing 3rd doses in patients with IMID. In our second study in this series, we examined the effects of 3rd doses on immune responses at 2-4 weeks following 3rd vaccination and saw that the decreased T-cell stimulation that occurs after 2nd doses was restored overall following a 3rd 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 3rd and 4th 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 4th 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 4th 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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Third and Fourth Vaccine Doses Broaden and Prolong Immunity to SARS-CoV-2 in Adult Patients with Immune-Mediated Inflammatory Diseases. Michelle W. Cheung, Roya M. Dayam, Janna R. Shapiro, Jaclyn C. Law, Gary Y. C. Chao, Daniel Pereira, Rogier L. Goetgebuer, David Croitoru, Joanne M. Stempak, Lily Acheampong, Saima Rizwan, Jenny D. Lee, Liz Jacob, Darshini Ganatra, Ryan Law, Victoria E. Rodriguez-Castellanos, Madeline Kern-Smith, Melanie Delgado-Brand, Genevieve Mailhot, Nigil Haroon, Robert D. Inman, Vincent Piguet, Vinod Chandran, Mark S. Silverberg, Tania H. Watts, Anne-Claude Gingras. The Journal of Immunology. 2023.06.16.265708; https://journals.aai.org/jimmunol/article/211/3/351/265708/Third-and-Fourth-Vaccine-Doses-Broaden-and-Prolong