Humoral and T-cell responses to SARS-CoV-2 vaccination in multiple sclerosis patients treated with ocrelizumab

Abstract

Background: The COVID-19 epidemic raises important questions about the efficacy of vaccines for people treated with ocrelizumab, an anti-CD20 therapy. Ocrelizumab has been shown to reduce the humoral response to SARS-CoV-2 infection and vaccination, but the T-cell response to vaccination has not been fully characterized. We sought to provide data regarding B and T-cell mediated responses to SARS-CoV-2 vaccination in ocrelizumab-treated patients, and to determine what variables correlate with vaccine immunogenicity. We hypothesized that patients without a humoral response to SARS-CoV-2 vaccination would still have intact T-cell responses.

Methods: We conducted a prospective, observational, single center cohort study of patients with MS treated with either ocrelizumab or natalizumab as a comparator between March 2, 2021, and July 1, 2021. Eligible patients were age 18 to 55 and had no known prior infection with, or vaccination against, SARS-CoV-2. Patients with prior use of immunosuppressive or chemotherapeutic agents, or treatment with any anti-CD20 therapy other than ocrelizumab within 12 months of enrollment, were excluded. The Roche Elecsys anti-SARS-CoV-2 S immunoassay was performed prior to and 3-4 weeks post vaccination to evaluate the antibody response to SARS-CoV-2 spike IgG. The Adaptive Biotechnologies T-Detect COVID Test was performed to evaluate the adaptive T-cell immune response to SARS-CoV-2 in OCR-treated patients with no detectable antibodies. Data were analyzed using descriptive statistics, Fisher's exact test, and Wilcoxon rank sum.

Results: Forty-eight patients were enrolled in the study, 69% treated with ocrelizumab and 31% treated with natalizumab. Eighteen percent of ocrelizumab and 100% of natalizumab patients had a positive antibody response. In ocrelizumab-treated patients, there was no correlation between age, sex, BMI, total number of infusions, immunoglobulin G, CD19, or absolute lymphocyte count and antibody response. There was a trend suggesting that a longer interval between the last infusion and vaccination increased the likelihood of producing antibodies (P = 0.062). All ocrelizumab patients with negative antibody responses had positive T-cell responses.

Conclusions: Treatment with ocrelizumab substantially impaired the humoral response to SAR-CoV-2 vaccination but did not impair T-cell responses. Further research is needed to determine if the T-cell response to SARS-CoV-2 vaccination is sufficient to prevent infection or reduce severity of COVID in patients who did not produce antibodies.

Keywords: COVID-19; Coronavirus vaccine; Immunogenicity; Multiple sclerosis; Natalizumab; Ocrelizumab; SARS-CoV-2.