Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Nat Med. 2021 Nov;27(11):1990-2001. doi: 10.1038/s41591-021-01507-2. Epub 2021 Sep 14.


SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Viral / analysis
  • Antibodies, Viral / blood
  • Antigens, CD20 / immunology
  • COVID-19 / prevention & control
  • COVID-19 Vaccines / therapeutic use*
  • Case-Control Studies
  • Chlorocebus aethiops
  • HEK293 Cells
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral / drug effects
  • Immunity, Humoral / physiology
  • Immunotherapy / methods
  • Longitudinal Studies
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / therapy*
  • RNA, Messenger / immunology
  • RNA, Viral / immunology
  • Rituximab / pharmacology
  • Rituximab / therapeutic use
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • Vaccination
  • Vero Cells


  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Antigens, CD20
  • COVID-19 Vaccines
  • RNA, Messenger
  • RNA, Viral
  • Rituximab

Grant support