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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.
- rituximab
- vaccination
- Covid-19
Data availability statement
Data are available upon reasonable request. Anonymous patient data is available under specific conditions. Proposals will be reviewed and approved by the sponsor, scientific committee and staff on the basis of scientific merit and the absence of competing interests. Once the proposal has been approved, data can be transferred through a secure online platform after the signing of a data access agreement and a confidentiality agreement.
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Data availability statement
Data are available upon reasonable request. Anonymous patient data is available under specific conditions. Proposals will be reviewed and approved by the sponsor, scientific committee and staff on the basis of scientific merit and the absence of competing interests. Once the proposal has been approved, data can be transferred through a secure online platform after the signing of a data access agreement and a confidentiality agreement.
Footnotes
Handling editor Gerd-Rüdiger R Burmester
MB and DM contributed equally.
Contributors All authors revised the manuscript and were involved in editing or quality control. MB, DA, DS, DM, MZ, ST and SW contributed to the study design. DM, HR, LH and DS contributed to data analysis. TP, HH and KS performed antibody measurements. JHA, MK, MM and PH contributed to cellular assays. MB, DA, JSS, DM, DS, LXH and MZ contributed to the first manuscript draft. ST, DM, MB, PM, BK, ES, RF-S, KR and EH-M contributed to patient recruitment. RT determined leucocyte subsets. MZ performed randomisation. MB and DM had access to all the data, accept full responsibility for the work and conduct of the study and controlled the decision to publish.
Funding Provision of vaccines and laboratory testing was provided free of charge by the City of Vienna and the Medical University of Vienna via the Vienna General Hospital. Laboratory testing was supported by the Medical-Scientific fund of the Mayor of the federal capital Vienna to JHA (grant number: Covid003). Otherwise, there was no specific funding or grant for this research from any funding agency in the public, commercial or not-for-profit sectors. The funders had no role in considering the study design or in the collection, analysis or interpretation of data, the writing of the report or the decision to submit the article for publication.
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.
Provenance and peer review Not commissioned; externally peer reviewed.
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