SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity

Ann Rheum Dis. 2021 Oct;80(10):1345-1350. doi: 10.1136/annrheumdis-2021-220781. Epub 2021 Jul 20.

Abstract

Objectives: Evidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation.

Methods: Patients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls.

Results: All healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p<0.001). Patients without detectable CD19+ peripheral B cells (n=36) did not develop specific antibodies, except for one patient. Circulating B cells correlated with the levels of antibodies (τ=0.4, p<0.001). However, even patients with a low number of B cells (<1%) mounted detectable SARS-CoV-2-specific antibody responses. SARS-CoV-2-specific T cells were detected in 58% of the patients, independent of a humoral immune response.

Conclusions: The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.

Keywords: COVID-19; rituximab; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antirheumatic Agents / therapeutic use*
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • B-Lymphocytes / immunology
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / immunology*
  • Female
  • Humans
  • Immunity, Cellular / immunology
  • Immunity, Humoral / immunology
  • Immunocompromised Host / immunology*
  • Immunogenicity, Vaccine / drug effects
  • Immunogenicity, Vaccine / immunology*
  • Male
  • Middle Aged
  • Rituximab / therapeutic use*
  • SARS-CoV-2
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antirheumatic Agents
  • COVID-19 Vaccines
  • Rituximab