ABSTRACT
BackgroundKnowledge about humoral and cellular immunogenicity and their kinetics following SARS-CoV-2 mRNA vaccinations in immunosuppressed patients is limited. MethodsAntibody and cytokine responses were assessed in 263 patients with either solid tumors (SOT, n=63), multiple myeloma (MM, n=70) or inflammatory bowel diseases (IBD, n=130) undergoing various immunosuppressive regimens and from 66 healthy controls before the first and the second, as well as four weeks and 5-6 months after the second mRNA vaccine dose with either BNT162b2 or mRNA-1273. FindingsFour weeks after the second dose, seroconversion was lower in cancer than in IBD patients and controls, with the highest non-responder rate in MM patients (17.1%). S1-specific IgG levels correlated with neutralizing antibody titers. While antibody responses correlated with cellular responses in controls and IBD patients, IFN-{gamma} and antibody responses did not in SOT and MM patients. At six months, 19.6% of patients with MM and 7.3% with SOT had become seronegative, while IBD patients and controls remained seropositive in 96.3% and 100%, respectively. Vaccinees receiving mRNA-1273 presented higher antibody levels than those vaccinated with BNT162b2. InterpretationCancer patients may launch an inadequate seroresponse in the immediate time range following vaccination and up to six months, correlating with vaccine-specific cellular responses. These findings propose antibody testing in immunosuppressed - along with cellular testing - provides guidance for administration of additional vaccine doses, or may indicate the necessity for antibody treatment. IBD patients respond well to the vaccine, but treatment such as with TNF- inhibitors may reduce persistence of immune responses. FundingThe study was sponsored and financed by the Medical University of Vienna - third party funding by the Institute of Specific Prophylaxis and Tropical Medicine. AOR. and HS acknowledge funding by the Austrian Science Fund (FWF, P 34253-B).
ABSTRACT
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination. In this blinded randomized clinical trial (EudraCT 2021-002348-57) 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 four. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at weeks one and four. Seroconversion rates at week four were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccine (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. No serious adverse events, related to immunization, were observed. 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.
