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Randomized Controlled Trial
. 2022 May;81(5):687-694.
doi: 10.1136/annrheumdis-2021-221558. Epub 2022 Jan 13.

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

Michael Bonelli #  1 , Daniel Mrak #  1 , Selma Tobudic  2 , Daniela Sieghart  1 , Maximilian Koblischke  3 , Peter Mandl  1 , Barbara Kornek  4 , Elisabeth Simader  1 , Helga Radner  1 , Thomas Perkmann  5 , Helmuth Haslacher  5 , Margareta Mayer  3 , Philipp Hofer  6 , Kurt Redlich  7 , Emma Husar-Memmer  8 , Ruth Fritsch-Stork  8   9 , Renate Thalhammer  5 , Karin Stiasny  3 , Stefan Winkler  2 , Josef S Smolen  1 , Judith H Aberle  3 , Markus Zeitlinger  10 , Leonhard X Heinz  1 , Daniel Aletaha  11
Affiliations
Randomized Controlled Trial

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

Michael Bonelli et al. Ann Rheum Dis. 2022 May.

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.

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Conflict of interest statement

Competing interests: BK has received honoraria for lecturing/consulting from Biogen, BMS Celgene, Johnson & Johnson, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. PM reports speaker fees from AbbVie, Janssen and Novartis and research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB. MB reports about personal fees from Eli-Lilly. DA received grants and consulting fees from AbbVie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche and Sandoz. JSS reports about grants, consulting and personal fees from AbbVie, Astra-Zeneca, Lilly, Novartis, Amgen, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung and UCB. KS received a research grant from Pfizer. MZ received grants and consulting fees from Nabriva, AntibioTxApS, Shionogi, NovoNordisk, Merck, Infectopharm and Pfizer. HH received grants from Glock Health, BlueSky Immunotherapies and Neutrolis. All other authors declare no competing interests.

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