THE T-CELL RESPONSE TO SARS-COV-2 VACCINATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE IS OFTEN DEFICIENT IN ANTIBODY-RESPONDERS, AND AUGMENTED BY ANTI-TNF THERAPY
Gastroenterology
; 162(7):S-675-S-676, 2022.
Article
in English
| EMBASE | ID: covidwho-1967359
ABSTRACT
Background:
Vaccination against SARS-CoV-2 is a highly effective strategy to protect against infection, which is predominantly mediated by vaccine-induced antibodies. Postvaccination antibodies are robustly produced by those with inflammatory bowel disease (IBD) even on immune-modifying therapies but are blunted by anti-TNF therapy. In contrast, T-cell response which primarily determines long-term efficacy against disease progression, , is less well understood. We aimed to assess the post-vaccination T-cell response and its relationship to antibody responses in patients with inflammatory bowel disease (IBD) on immunemodifying therapies.Methods:
We evaluated IBD patients who completed SARS-CoV-2 vaccination using samples collected at four time points (dose 1, dose 2, 2 weeks after dose 2, 8 weeks after dose 2). T-cell clonal analysis was performed by T-cell Receptor (TCR) immunosequencing. The breadth (number of unique sequences to a given protein) and depth (relative abundance of all the unique sequences to a given protein) of the T-cell clonal response were quantified using reference datasets and were compared to antibody responses.Results:
Overall, 303 subjects were included (55% female;5% with prior COVID) (Table). 53% received BNT262b (Pfizer), 42% mRNA-1273 (Moderna) and 5% Ad26CoV2 (J&J). The Spike-specific clonal response peaked 2 weeks after completion of the vaccine regimen (3- and 5-fold for breadth and depth, respectively);no changes were seen for non-Spike clones, suggesting vaccine specificity. Reduced T-cell clonal depth was associated with chronologic age, male sex, and immunomodulator treatment, and was preserved by nonanti- TNF biologic therapies;augmented clonal depth was associated with anti-TNF treatment (Figure). TCR depth and breadth were associated with vaccine type;after adjusting for age and gender, Ad26CoV2 (J&J) exhibited weaker metrics than mRNA-1273 (Moderna) (p= 0.01 for each) or BNT262b (Pfizer) (p=0.056 for depth). Antibody and T-cell responses were only modestly correlated;while those with robust humoral responses also had robust TCR clonal expansion, a substantial fraction of patients with high antibody levels had only a minimal T-cell clonal response (Figure).Conclusion:
Age, sex and select immunotherapies are associated with the T-cell clonal response to SARS-CoV-2 vaccines, and T-cell responses are low in many patients despite high antibody levels. These factors, as well as differences seen by vaccine type may help guide reimmunization vaccine strategy in immune-impaired populations. Further study of the effects of anti-TNF therapy on vaccine responses are warranted. (Table Presented)
elasomeran; endogenous compound; immunomodulating agent; T lymphocyte receptor; tumor necrosis factor; adult; age; antibody response; clinical evaluation; conference abstract; controlled study; coronavirus disease 2019; drug therapy; female; gender; human; human tissue; humoral immunity; immunization; immunotherapy; inflammatory bowel disease; major clinical study; male; nonhuman; Severe acute respiratory syndrome coronavirus 2; spike; T lymphocyte; vaccination
Full text:
Available
Collection:
Databases of international organizations
Database:
EMBASE
Topics:
Vaccines
Language:
English
Journal:
Gastroenterology
Year:
2022
Document Type:
Article
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