Humoral and T-Cell Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Ocrelizumab

Abstract

IMPORTANCE B-cell-depleting therapies may affect the development of a protective immune response following vaccination. Understanding the ability to develop vaccine-specific immunity to COVID-19 in patients with multiple sclerosis (MS) treated with B-cell-depleting therapy is of importance for clinical decisions. OBJECTIVE To assess SARS-CoV-2 vaccine-specific humoral and cellular responses in patients treated with ocrelizumab compared with healthy controls. DESIGN, SETTING, AND PARTICIPANTS This single-center study performed at Hadassah Medical Center in Jerusalem, Israel, included patients with MS treated with ocrelizumab, healthy controls, and untreated patients with MS. Vaccination occurred between December 2020 and April 2021. Participants donated blood 2 to 4 and 2 to 8 weeks after the second vaccine dose for antibody and T-cell assessments, respectively. EXPOSURES All participants received 2 doses of BNT162b2 vaccine (Pfizer/BioNTech) and completed the study. MAIN OUTCOMES AND MEASURES Proportion of patients treated with ocrelizumab with SARS-CoV-2-specific serology and/or T-cell responses following vaccination. All participants underwent SARS-CoV-2 antibody testing; 29 patients treated with ocrelizumab and 15 healthy controls had evaluation of SARS-CoV-2-specific T-cell responses.RESULTS Of 112 participants, 49 (43.8%) had MS and were treated with ocrelizumab (33 [67.3%] female; mean [SD] age, 47.9 [13.3] years), 23 (20.5%) had MS and were not treated with disease-modifying therapies (18 [78.3%] female; mean [SD] age, 49 [13.4] years), and 40 (35.7%) were healthy controls (25 [62.5%] female; mean [SD] age, 45.3 [16] years). Twenty-six of 29 patients (89.7%) treated with ocrelizumab and 15 of 15 healthy controls (100%) had SARS-CoV-2-specific T cells following vaccination at similar levels (mean [SD], 15.4 [7.6] and 14.3 [6.3] spot-forming cells, respectively). Mean antibody titers and positive serology rate were lower in the group of patients treated with ocrelizumab (mean [SD] antibody titers and positive serology rate, 26.2 [49.2] and 376.5 [907.6] AU/mL; 10 of 40 [25%] and 20 of 49 [40.8%] for S1/S2 and receptor-binding domain, respectively) compared with healthy controls (mean [SD] antibody titers and positive serology rate, 283 [100] and 12 712 [9114] AU/mL; 100% S1/S2 and receptor-binding domain) and untreated patients (mean [SD] antibody titers and positive serology rate, 288.3 [113.

Preserved T cell responses to SARS-CoV-2 in anti-CD20 treated multiple sclerosis

“…Our current findings extend previous work showing diminished humoral immune responses to SARS-CoV-2 vaccinations in anti-CD20 treated pwMS 8,13,14,22 by demonstrating that not only antibody levels, but also the functionality of SARS-CoV-2 antibodies is reduced in anti-CD20 treated pwMS. Of note, the diminished avidity of SARS-CoV-2 antibodies suggests that B cell depletion by anti-CD20 therapies interferes with normal antibody maturation, which appears relevant also for other vaccinations in patients treated with anti-CD20 therapies.…”

“…Remarkably, all anti-CD20 treated pwMS vaccinated twice and all SARS-CoV-2 infected pwMS in whom T cell responses could be tested had SARS-CoV-2 specific T cells. Together with very recent similar results 6,13,14 , these data suggest that B cell depletion in anti-CD20 treated pwMS does not impair the generation of SARS-CoV-2 specific cellular immune responses. As an early and robust SARS-CoV-2 specific T cell response is associated with mild or asymptomatic SARS-CoV-2 infections even in the absence of antibodies 26,27 , our findings indicate that SARS-CoV-2 vaccination of anti-CD20 treated pwMS may result in some degree of protection from COVID-19.…”

“…While very recent studies suggest that SARS-CoV-2 specific T cellular immune responses may be preserved in pwMS under anti-CD20 therapy, given the importance of these findings, independent confirmation appears warranted. 13,14 The first laboratory-confirmed patient with COVID-19 in Germany was reported on January 27, 2020. 15 To monitor SARS-CoV-2 specific humoral immune responses in anti-CD20 treated pwMS, we started to prospectively collect sera for SARS-CoV-2 antibody determinations from pwMS treated with anti-CD20 therapies at the MS outpatient clinic, Charité Campus Mitte, Charité -Universitätsmedizin Berlin, Germany, on March 5, 2020.…”

COVID-19 susceptibility and outcomes among patients with neuromyelitis optica spectrum disorder (NMOSD): A systematic review and meta-analysis

“…Of particular concern is the effect of disease-modifying therapies (DMTs) and immunosuppressive therapies on vaccine effectiveness. Studies show poor antibody production following the COVID-19 infection and administration of mRNA vaccine in MS and NMOSD patients treated with anti-CD20 agents ( Apostolidis et al, 2021 ; Bigaut et al, 2021 ; Brill et al, 2021 ; Louapre et al, 2021 ). On the othe hand these patients generated robust SARS-CoV-2 specific T-cell responses following the vaccination ( Apostolidis et al, 2021 ; Brill et al, 2021 ).…”

“…Studies show poor antibody production following the COVID-19 infection and administration of mRNA vaccine in MS and NMOSD patients treated with anti-CD20 agents ( Apostolidis et al, 2021 ; Bigaut et al, 2021 ; Brill et al, 2021 ; Louapre et al, 2021 ). On the othe hand these patients generated robust SARS-CoV-2 specific T-cell responses following the vaccination ( Apostolidis et al, 2021 ; Brill et al, 2021 ). Treatment with DMTs has not been linked to an impaired response to SARS-CoV-2 vaccine ( Jena et al, 2021 ).…”