AUTHOR=Xu Alexander M. , Li Dalin , Ebinger Joseph E. , Mengesha Emebet , Elyanow Rebecca , Gittelman Rachel M. , Chapman Heidi , Joung Sandy , Botwin Gregory J. , Pozdnyakova Valeriya , Debbas Philip , Mujukian Angela , Prostko John C. , Frias Edwin C. , Stewart James L. , Horizon Arash A. , Merin Noah , Sobhani Kimia , Figueiredo Jane C. , Cheng Susan , Kaplan Ian M. , McGovern Dermot P. B. , Merchant Akil , Melmed Gil Y. , Braun Jonathan 

TITLE=Differences in SARS-CoV-2 Vaccine Response Dynamics Between Class-I- and Class-II-Specific T-Cell Receptors in Inflammatory Bowel Disease

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.880190

DOI=10.3389/fimmu.2022.880190

ISSN=1664-3224

ABSTRACT=Over the course of the COVID-19 pandemic, vulnerable populations such as the immunocompromised were identified, vaccinated, and heavily monitored. Remarkably, one group of the immunocompromised – patients with inflammatory bowel disease (IBD) – mounted vigorous immune responses to vaccines, comparable to healthy individuals. How these patients, who experience strong immunomodulatory treatments such as anti-TNF stimulation, respond to the vaccine is unknown. Here we used T-cell receptor sequencing to show that T-cell responses in an IBD cohort were influenced by demographic and immune factors, relative to a healthy cohort of health care workers (HCWs).  Blood samples were longitudinally collected around vaccination timepoints, and the TCR Vβ gene repertoires were sequenced and analyzed for COVID-19-specific clones. We observed significant age and vaccine type differences in the overall strength of the T-cell response. We further stratified the T-cell response into Class-I- and Class-II-specific responses, showing that traditional vaccines induced Class-I-biased T-cell responses and mRNA vaccine types led to differential responses, with Moderna’s mRNA-1273 vaccine inducing a more Class-I-deficient T-cell response. Finally, we showed that these T-cell patterns were consistent with antibody serology from the same patients. Our results account for the surprising success of vaccination in nominally immuno-compromised IBD patients, while suggesting vaccination guidelines for IBD patients prone to deficiencies in T-cell response.