NVX-CoV2373-induced T- and B-cellular immunity in immunosuppressed people with multiple sclerosis that failed to respond to mRNA and viral vector SARS-CoV-2 vaccines.

Immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is important, especially in people with multiple sclerosis (pwMS) on immunosuppressive therapies. This study aims to determine whether adjuvanted protein-based vaccine NVX-CoV2373 is able to induce an immune response to SARS-CoV-2 in pwMS with inadequate responses to prior triple mRNA/viral vector vaccination. We conducted a single-center, prospective longitudinal cohort study at the MS Center in Dresden, Germany. In total, 65 participants were included in the study in accordance with the following eligibility criteria: age > 18 years, immunomodulatory treatment, and insufficient T-cellular and humoral response to prior vaccination with at least two doses of SARS-CoV-2 mRNA (BNT162b2, mRNA-1273) or viral vector vaccines (AZD1222, Ad26.COV2.S). Intramuscular vaccination with two doses of NVX-CoV2373 at baseline and 3 weeks of follow-up. The development of SARS-CoV-2-specific antibodies and T-cell responses was evaluated. For the final analysis, data from 47 patients on stable treatment with sphingosine-1-phosphate receptor (S1PR) modulators and 17 on ocrelizumab were available. The tolerability of the NVX-CoV2373 vaccination was overall good and comparable to the one reported for the general population. After the second NVX-CoV2373 vaccination, 59% of S1PR-modulated patients developed antispike IgG antibodies above the predefined cutoff of 200 binding antibody units (BAU)/ml (mean, 1,204.37 [95% CI, 693.15, 2,092.65] BAU/ml), whereas no clinically significant T-cell response was found. In the subgroup of the patients on ocrelizumab treatment, 23.5% developed antispike IgG > 200 BAU/ml (mean, 116.3 [95% CI, 47.04, 287.51] BAU/ml) and 53% showed positive spike-specific T-cellular responses (IFN-gamma release to antigen 1: mean, 0.2 [95% CI, 0.11, 0.31] IU/ml; antigen 2: mean, 0.24 [95% CI, 0.14, 0.37]) after the second vaccination. Vaccination with two doses of NVX-CoV2373 was able to elicit a SARS-CoV-2-specific immune response in pwMS lacking adequate immune responses to previous mRNA/viral vector vaccination. For patients receiving S1PR modulators, an increase in anti-SARS-CoV-2 IgG antibodies was detected after NVX-CoV2373 vaccination, whereas in ocrelizumab-treated patients, the increase of antiviral T-cell responses was more pronounced. Our data may impact clinical decision-making by influencing the preference for NVX-CoV2373 vaccination in pwMS receiving treatment with S1PR modulation or anti-CD20 treatment.

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Copyright © 2023 Mueller-Enz, Woopen, Katoul Al Rahbani, Haase, Dunsche, Ziemssen and Akgün.

Déclaration de conflit d'intérêts

KA received personal compensation for consulting services and speaker honoraria from Roche, Novartis, Merck, Sanofi, Teva, BMS, Biogen, and Celgene. TZ received personal compensation for consulting services and speaker honoraria from Biogen Idec, Bayer, Novartis, Sanofi, Teva, and Synthon. TZ received additional financial support for research activities from Bayer, Biogen Idec, Novartis, Teva, and Sanofi Aventis. CW received travel support from Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.