Ulf Geisen1, Ruben Rose2, Dennis Berner3, Hayley Reid3, Jan Schirmer4, Florian Tran5, Sascha Gerdes6, Stefan Schreiber7, Andi Krumbholz1, Petra Bacher7 and Bimba Hoyer1, 1UKSH Kiel, Kiel, Germany, 2Dep Infectiology UKSH Kiel, Kiel, Germany, 3Dep Rheumatology and clinical Immunology, UKSH Kiel, Kiel, Germany, 4University Medical Center Schleswig-Holstein, Kiel, Germany, 5Medical Department, UKSH Kiel, Kiel, Germany, 6Dermatology, UKSH Kiel, Kiel, Germany, 7Institute of Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
Background/Purpose: Background: The ongoing pandemic is an immunological challenge when using immune modulating drugs. The mRNA vaccines against SARS-CoV-2 are safe and efficient in most patients using these drugs, at least in short-time observations. Despite very aggressive therapy like high dose corticosteroids or B cell depleting therapy, little is known about the underlying effects.
Objectives: In this work we show that SARS-CoV-2 antibody quantities and quality decreases dramatically 6 months after the second vaccination compared to patients using other DMARDs and healthy controls but are restored after the third vaccination. In addition, changes in B and T cell compartment underline this serological observation
Methods: 25 patients with chronic inflammatory diseases and 25 healthy controls were recruited from health care workers. All individuals signed informed consent and the study was approved by the local ethics committee. In serum samples, SARS-COV-2 IgG was analysed by ELISA, avidity by blot and neutralisation using a live vero cell assay. B cell and T cell subsets were analysed from PBMCs using flow cytometry. For T cells, antigen reactive T cell enrichment was performed.
Results: 7-14 days after the vaccination, all patients showed promising SARS-CoV-2 IgG serum levels as well as good antibody avidity and neutralisation against the wuhan strain. 6 months later, antibody levels as well as avidity and neutralisation in patients using TNF inhibitors delined more than in controls. On plasma cell level, we could see that patients using TNF inhibitors have comparable absolute plasma cell counts for spike protein specific cells but a higher number of plasma cells of other specificities i.e. Bystander reaction. SARS-CoV-2 specific CD4 T cell populations showed a tendency to have more TNFa and IL21 producing cells directly after the vaccination.
Conclusion: Patients using TNF blockers show an altered plasma cell compartment after SARS-CoV-2 vaccination, leading to the assumption, that the vaccine reaction is less specific and less targeted than in healthy controls and in patients using other DMARDs, however seems to be ameliorated by a third dose. Further research will include the analysis of antibody glycosylation and affinity to newer variants.
Disclosures: U. Geisen, None; R. Rose, None; D. Berner, None; H. Reid, None; J. Schirmer, None; F. Tran, None; S. Gerdes, None; S. Schreiber, None; A. Krumbholz, None; P. Bacher, None; B. Hoyer, None.
