Primary ChAdOx1 vaccination fails to reactivate pre-existing, cross-reactive T cells
HENZE L. 2,3, BRAUN J. 2,3, MEYER-ARNDT L. 2,3,4,5, JÜRCHOTT K. 2,3, SCHLOTZ M. 6, MICHEL J. 7, GROSSEGESSE M. 7, MANGOLD M. 2,3, DINGELDEY M. 2,3, KRUSE B. 2,3, HOLENYA P. 8, MAGES N. 2,3,9, REIMER U. 8, ECKEY M. 8, TIMMERMANN B. 9, KLEIN F. 6,10,11, NITSCHE A. 7, GIESECKE-THIEL C. 9, LOYAL L. 2,3, THIEL A. 2,3
1 BIH Charité, Si-M, Berlin, Germany; 2 Si-M/”Der Simulierte Mensch” a science framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; 3 Regenerative Immunology and Aging, BIH Immunomics, Berlin Institute of Health, Berlin, Germany; 4 NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 5 Department of Neurology with Experimental Neurology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 6 Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; 7 Highly Pathogenic Viruses, Centre for Biological Threats and Special Pathogens, WHO Reference Laboratory for SARS-CoV-2 and WHO Collaborating Centre for Emerging Infections and Biological Threats, Robert Koch Institute, Berlin, Germany; 8 JPT Peptide Technologies GmbH, Berlin, Germany; 9 Max Planck Institute for Molecular Genetics, Berlin, Germany; 10 German Center for Infection Research (DZIF), Partner site Bonn-Cologne, Cologne, Germany; 11 Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
Current vaccination schemes against SARS-CoV-2 include mRNA-, vector- or protein plus adjuvants-based vaccines targeting the spike protein as well as attenuated virus and are considered a key strategy to control the pandemic. While BNT162b2-mRNA (Comirnaty, BioNTech/Pfizer) vaccination reactivates pre-existing, pan-coronavirus-specific, cross-reactive immunity, the effect of vector vaccines in this respect is unknown. Here we monitored cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (Vaxzeria, AstraZeneca)/BNT162b2 vaccination and compare it to homologous BNT162b2 vaccination regimens. Vector-based primary vaccination failed to efficiently reactivate cross-reactive cellular and humoral immune responses as compared to mRNA vaccination. After secondary vaccination T cell responses were comparable and the antibody titers higher in heterologous vaccinated, however the neutralizing capacity against the immune escape variant Omicron BA.5 was reduced. Our data demonstrates that vector- and mRNA-vaccination elicit distinct patterns of cross-reactive adaptive immune responses with implications in the development of future pan-coronavirus vaccines.