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 [113.8] and 10 877 [9476] AU/mL; 100% S1/S2 and receptor-binding domain), with positive association to time from ocrelizumab infusion (S1/S2: r = 0.7, P < .001; receptor-binding domain: r = 0.4, P = .04).

Conclusion and relevance: In this study, patients with MS who were treated with ocrelizumab generated comparable SARS-CoV-2-specific T-cell responses with healthy controls and had lower antibody response following vaccination. Given the potential role of T cells in protection from severe disease, this is reassuring and will help physicians develop consensus guidelines regarding MS treatment in the era of the COVID-19 pandemic.

Figure 1.. SARS-CoV-2 Messenger RNA Vaccine Antibody Response in Patients With Multiple Sclerosis Treated With Ocrelizumab

Serology response to SARS-CoV-2 messenger RNA vaccine. A, SARS-CoV-2 anti-S1/S2 IgG titers 2 to 4 weeks postvaccine in healthy controls (n = 40): mean (SD), 283 (100) AU/mL; patients with multiple sclerosis (MS) not treated (n = 23): mean (SD), 288.3 (113.8) AU/mL; patients with MS treated with ocrelizumab (OCR) (n = 40): mean (SD), 26.2 (49.2) AU/mL (P < .001). B, SARS-CoV-2 anti–receptor-binding domain (RBD) IgG titers 2 to 4 weeks after vaccination in healthy controls (n = 35): mean (SD), 12 712 (9114) AU/mL; patients with MS not treated (n = 20): mean (SD), 10 877 (9476); and patients treated with OCR (n = 49): mean (SD), 376.5 (907.6) AU/mL. The dotted line indicates positive threshold (≥19 and ≥50 AU/mL in the Liaison and Architect assay, respectively). Horizontal bars indicate the mean. C, SARS-CoV-2 anti-S1/S2 antibody titers of patients with MS treated with OCR (n = 8) at 2 time points (3 and 8 weeks after vaccination). AU indicates arbitrary units. ^aValues were significant (P < .001).

Figure 2.. SARS-CoV-2 Spike-Specific T-Cell Response Following Vaccination

Postvaccination T-cell response to SARS-CoV-2 spike protein peptides. Wells stimulated with SARS-CoV-2 spike peptides as measured by an interferon γ enzyme-linked immunospot. Each participant’s peripheral blood mononuclear cells are placed into 4 wells (250 000 cells per well) where they are exposed to nil control and 2 separate panels of SARS-CoV-2 antigens containing overlapping peptides spanning sequences derived from spike and nucleocapsid proteins and a phytohemagglutinin control. A, SARS-CoV-2–specific T-cell response of healthy controls (n = 15) and patients with multiple sclerosis (MS) treated with ocrelizumab (OCR) (n = 29) postvaccination and 5 healthy controls prevaccine as measured by T-SPOT (Oxford Immunotec). Spot-forming cells (SFCs) per 250 000 cells for each participant represent the number of T cells specific to spike SARS-CoV-2. B, T-cell response postvaccination of patients with MS treated with OCR who had positive SARS-CoV-2 IgG (IgG+) or negative SARS-CoV-2 (IgG−). Ten of 11 patients with MS treated with OCR who had positive serology response were also positive for T-cell response (mean [SD] SFC, 14.5 [7.4]). Sixteen of 18 patients with negative serology response had positive specific T-cell response (mean [SD], 15.9 [7.9]). The dotted line indicates positive threshold (SFC, ≥6). Horizontal bars indicate the mean.