Journal Article

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

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

2022

Overview

T-cells specifically bind antigens to induce adaptive immune responses using highly specific molecular recognition, and a diverse T-cell repertoire with expansion of antigen-specific clones can indicate robust immune responses after infection or vaccination. For patients with inflammatory bowel disease (IBD), a spectrum of chronic intestinal inflammatory diseases usually requiring immunomodulatory treatment, the T-cell response has not been well characterized. Understanding the patient factors that result in strong vaccination responses is critical to guiding vaccination schedules and identifying mechanisms of T-cell responses in IBD and other immune-mediated conditions. 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 control cohort of health care workers (HCWs). Subjects were sampled at the time of SARS-CoV-2 vaccination, and longitudinally afterwards; TCR Vβ gene repertoires were sequenced and analyzed for COVID-19-specific clones. We observed significant differences in the overall strength of the T-cell response by age and vaccine type. We further stratified the T-cell response into Class-I- and Class-II-specific responses, showing that Ad26.COV2.S vector vaccine induced Class-I-biased T-cell responses, whereas mRNA vaccine types led to different responses, with mRNA-1273 vaccine inducing a more Class-I-deficient T-cell response compared to BNT162b2. Finally, we showed that these T-cell patterns were consistent with antibody levels from the same patients. Our results account for the surprising success of vaccination in nominally immuno-compromised IBD patients, while suggesting that a subset of IBD patients prone to deficiencies in T-cell response may warrant enhanced booster protocols.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: 2019-nCoV Vaccine mRNA-1273 / Ad26COVS1 / Age / Antibodies / Antigens / BNT162 Vaccine / COVID-19 / COVID-19 Vaccines / Generalized linear models / Hispanic Americans / Humans / Immune response / Immunity, Humoral / immunodeficiency / Immunology / Immunomodulation / Infections / Inflammatory bowel disease / Inflammatory Bowel Diseases / Intestine / Kinases / Lymphocytes T / Medical personnel / mRNA / mRNA vaccine / mRNA Vaccines / Patients / Receptors, Antigen, T-Cell - genetics / SARS-CoV-2 / SARS-CoV-2 (COVID-19) / Severe acute respiratory syndrome coronavirus 2 / Standard scores / Steroids / T cell receptors / T-cell repertoire / Vaccines / Vaccines, Synthetic