Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomised controlled trial

Ann Rheum Dis. 2022 May;81(5):687-694. doi: 10.1136/annrheumdis-2021-221558. Epub 2022 Jan 13.

Abstract

Objectives: SARS-CoV-2-induced COVID-19 has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination.

Methods: In this blinded randomised clinical trial, we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford-AstraZeneca). Patients were stratified according to the presence of peripheral B cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week 4. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at week 1 and week 4.

Results: Seroconversion rates at week 4 were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccines (p=0.6). Overall, 27% of patients seroconverted; specific T cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. 3/37 (8%) of patients without and 12/18 (67%) of the patients with detectable peripheral B cells seroconverted. No serious adverse events, related to immunisation, were observed.

Conclusions: This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.

Keywords: Covid-19; rituximab; vaccination.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • BNT162 Vaccine
  • COVID-19 Vaccines / adverse effects
  • COVID-19* / prevention & control
  • ChAdOx1 nCoV-19
  • Humans
  • RNA, Messenger
  • SARS-CoV-2*
  • Seroconversion
  • Vaccination
  • Vaccines, Synthetic
  • mRNA Vaccines

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • RNA, Messenger
  • Vaccines, Synthetic
  • mRNA Vaccine
  • mRNA Vaccines
  • ChAdOx1 nCoV-19
  • BNT162 Vaccine