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T cell response after SARS-CoV-2 vaccination in immunocompromised patients with inflammatory bowel disease.

ABSTRACT:

Background

Vaccination is a promising strategy to protect vulnerable groups like immunocompromised inflammatory bowel disease (IBD) patients from an infection with SARS-CoV-2. These patients may have lower immune responses. Little is known about the cellular and humoral immune response after a SARS-CoV-2 vaccination in IBD.

Methods

28 patients with IBD and 27 age- and sex-matched healthy controls were recruited at Jena University Hospital. Blood samples were taken before, after the first and in a subgroup of 11 patients after second dose of a SARS-CoV-2 vaccination. Cellular immune response including IFN-γ and TNF-α response and antibody titers were analyzed.

Results

Overall, 71.4% of the IBD-patients and 85.2% of the controls showed levels of anti-SARS-CoV-2 antibodies above the cutoff of 33.8 BAU/ml (p=0.329) after the first dose. Even in the absence of SARS-CoV-2 antibodies, IBD patients showed significant T cell responses after first SARS-CoV-2 vaccination compared to healthy controls, which was not influenced by different immunosuppressive regimens. Associated with the vaccination, we could also detect a slight increase of the TNF production among SARS-CoV-2-reactive TH cells in HD and IBD patients. After the second dose of vaccination, in IBD patients a further increase of humoral immune response in all but one patient was observed.

Conclusions

Already after the first dose of a SARS-CoV-2 vaccination, cellular immune response in IBD patients is comparable to controls, indicating a similar efficacy. However, close monitoring of long-term immunity in these patients should be considered.

SUBMITTER: Reuken PA

PROVIDER: S-EPMC8385945 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundVaccination 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 immune-modifying therapies.MethodsWe 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.ResultsOverall, 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. It was preserved by non-anti-TNF biologic therapies, and augmented clonal depth was associated with anti-TNF treatment. 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.ConclusionAge, 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.