The cellular immune response against Epstein-Barr virus decreases during ocrelizumab treatment

•Lymphocyte proliferation to autologous Epstein-Barr virus (EBV) infected cells decreases on treatment with ocrelizumab (OCR).•The number of cells secreting interferon-γ on stimulation with EBV or autologous EBV-infected cells also decreases on OCR.•Responses to varicella zoster virus, influenza virus, and a mitogen did not change.•The benefit of OCR for MS may be through removal of EBV antigen stimulus. Epstein‐Barr Virus (EBV) is strongly associated with multiple sclerosis (MS). After initial infection, EBV maintains a life‐long latent infection in B lymphocytes. Depletion of B lymphocytes from the blood with the anti-CD20 antibody ocrelizumab markedly reduces disease activity in MS. Our objective was to measure the effect of ocrelizumab treatment on the cellular immune response to EBV. Blood was collected from MS patients before and during ocrelizumab treatment. Peripheral blood mononuclear cells were stimulated with various antigens, and the response was measured using tritiated thymidine for proliferation and ELIspot for number of interferon-γ producing cells. The proliferation to autologous EBV-infected cells (LCL) was decreased after both 6 and 12 months of treatment. The number of interferon-γ producing cells on ELIspot in response to stimulation with either LCL or EBV also decreased. Responses to varicella zoster virus, influenza virus, and a mitogen did not change significantly. The cellular immune response to EBV and LCL decreases during treatment with ocrelizumab. The benefit of ocrelizumab for MS may be through removal of EBV antigenic stimulus. [Display omitted]