Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases

Ann Rheum Dis. 2022 May;81(5):720-728. doi: 10.1136/annrheumdis-2021-221508. Epub 2022 Jan 12.


Objectives: The emergence of strains of SARS-CoV-2 exhibiting increase viral fitness and immune escape potential, such as the Delta variant (B.1.617.2), raises concerns in immunocompromised patients. We aimed to evaluate seroconversion, cross-neutralisation and T-cell responses induced by BNT162b2 in immunocompromised patients with systemic inflammatory diseases.

Methods: Prospective monocentric study including patients with systemic inflammatory diseases and healthcare immunocompetent workers as controls. Primary endpoints were anti-spike antibodies levels and cross-neutralisation of Alpha and Delta variants after BNT162b2 vaccine. Secondary endpoints were T-cell responses, breakthrough infections and safety.

Results: Sixty-four cases and 21 controls not previously infected with SARS-CoV-2 were analysed. Kinetics of anti-spike IgG after BNT162b2 vaccine showed lower and delayed induction in cases, more pronounced with rituximab. Administration of two doses of BNT162b2 generated a neutralising response against Alpha and Delta in 100% of controls, while sera from only one of rituximab-treated patients neutralised Alpha (5%) and none Delta. Other therapeutic regimens induced a partial neutralising activity against Alpha, even lower against Delta. All controls and cases except those treated with methotrexate mounted a SARS-CoV-2 specific T-cell response. Methotrexate abrogated T-cell responses after one dose and dramatically impaired T-cell responses after two doses of BNT162b2. Third dose of vaccine improved immunogenicity in patients with low responses.

Conclusion: Rituximab and methotrexate differentially impact the immunogenicity of BNT162b2, by impairing B-cell and T-cell responses, respectively. Delta fully escapes the humoral response of individuals treated with rituximab. These findings support efforts to improve BNT162b2 immunogenicity in immunocompromised individuals ( number, NCT04870411).

Keywords: Covid-19; methotrexate; rituximab; vaccination.

Publication types

  • Clinical Study

MeSH terms

  • Antibodies, Viral
  • BNT162 Vaccine*
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Humans
  • Immunocompromised Host
  • Immunogenicity, Vaccine
  • Methotrexate
  • Prospective Studies
  • Rituximab
  • SARS-CoV-2


  • Antibodies, Viral
  • COVID-19 Vaccines
  • Rituximab
  • BNT162 Vaccine
  • Methotrexate

Supplementary concepts

  • SARS-CoV-2 variants

Associated data