Longitudinal T-Cell Responses After a Third SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis on Ocrelizumab or Fingolimod

Abstract

Objectives: To evaluate whether a third vaccination shows an added effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell responses in patients with multiple sclerosis treated with ocrelizumab or fingolimod.

Methods: This is a substudy of a prospective multicenter study on SARS-CoV-2 vaccination in patients with immune-mediated diseases. Patients with MS treated with ocrelizumab, fingolimod, and no disease-modifying therapies and healthy controls were included. The number of interferon (IFN)-γ secreting SARS-CoV-2-specific T cells at multiple time points before and after 3 SARS-CoV-2 vaccinations were evaluated.

Results: In ocrelizumab-treated patients (N = 24), IFN-γ-producing SARS-CoV-2-specific T-cell responses were induced after 2 vaccinations with median levels comparable to healthy controls (N = 12) and patients with MS without disease-modifying therapies (N = 10). A third vaccination in ocrelizumab-treated patients (N = 8) boosted T-cell responses that had declined after the second vaccination, but did not lead to higher overall T-cell responses as compared to immediately after a second vaccination. In fingolimod-treated patients, no SARS-CoV-2-specific T cells were detected after second (N = 12) and third (N = 9) vaccinations.

Discussion: In ocrelizumab-treated patients with MS, a third SARS-CoV-2 vaccination had no additive effect on the maximal T-cell response but did induce a boost response. In fingolimod-treated patients, no T-cell responses could be detected following both a second and third SARS-CoV-2 vaccination.

Figure. SARS-CoV-2–Specific T-Cell Responses Do Not Change Following a Third Vaccination Compared With the Response Following a Second SARS-CoV-2 Vaccination in Patients With MS Treated With Ocrelizumab or Fingolimod

Number of spike-specific IFN-γ–producing T cells (A) before vaccination and 1 week after a second vaccination (HC [n = 12], no DMT [n = 10], OCR [n = 24]), or 28 days after the second vaccination (FTY [n = 12]); and (B) after the second vaccination, before the third vaccination, and 1 week after the third vaccination in a selection of OCR-treated patients (n = 8) and FTY-treated patients (n = 9). Results are shown as the average number of spot-forming units (SFU) of S1 and S2 together per 2 × 10⁵ cells after subtracting the SFU of unstimulated wells. Three OCR-treated patients who seroconverted after the second vaccination had an SFU of 83, 48, and 0 (after the second vaccination). Samples not responding to the positive control and samples with too high background were excluded. *p < 0.05, **p < 0.01, and ****p < 0.0001. A Wilcoxon signed-rank test or Mann-Whitney U test was performed to compare differences in T-cell responses between paired and unpaired observations, respectively. R version 4.1.0 was used. DMT = disease-modifying therapy; FTY = fingolimod; HC = healthy control; IFN = interferon; MS = multiple sclerosis; OCR = ocrelizumab; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.