Comparative analysis of ChAdOx1 nCoV-19 and Ad26.COV2.S SARS-CoV-2 vector vaccines

Stephan Michalik; Florian Siegerist; Raghavendra Palankar; Kati Franzke; Maximilian Schindler; Alexander Reder; Ulrike Seifert; Clemens Cammann; Jan Wesche; Leif Steil; Christian Hentschker; Manuela Gesell-Salazar; Emil Reisinger; Martin Beer; Nicole Endlich; Andreas Greinacher; Uwe Völker

doi:10.3324/haematol.2021.280154

Comparative analysis of ChAdOx1 nCoV-19 and Ad26.COV2.S SARS-CoV-2 vector vaccines

Haematologica. 2022 Apr 1;107(4):947-957. doi: 10.3324/haematol.2021.280154.

Authors

Stephan Michalik¹, Florian Siegerist², Raghavendra Palankar³, Kati Franzke⁴, Maximilian Schindler², Alexander Reder¹, Ulrike Seifert⁵, Clemens Cammann⁵, Jan Wesche³, Leif Steil¹, Christian Hentschker¹, Manuela Gesell-Salazar¹, Emil Reisinger⁶, Martin Beer⁷, Nicole Endlich², Andreas Greinacher⁸, Uwe Völker⁹

Affiliations

¹ Interfaculty Institute of Genetics and Functional Genomics, Department Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
² Institute for Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany.
³ Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
⁴ Institute of Infectiology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
⁵ Friedrich Loeffler-Institute of Medical Microbiology-Virology, University Medicine Greifswald, Greifswald, Germany..
⁶ Division of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, Rostock University Medical Center, Rostock, Germany.
⁷ Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
⁸ Institute of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany. andreas.greinacher@med.unigreifswald.
⁹ Interfaculty Institute of Genetics and Functional Genomics, Department Functional Genomics, University Medicine Greifswald, Greifswald, Germany. voelker@uni-greifswald.de.

Abstract

Vector-based SARS-CoV-2 vaccines have been associated with vaccine- induced thrombosis with thrombocytopenia syndrome (VITT/TTS), but the causative factors are still unresolved. We comprehensively analyzed the ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Johnson and Johnson) vaccines. ChAdOx1 nCoV-19 contains significant amounts of host cell protein impurities, including functionally active proteasomes, and adenoviral proteins. A much smaller amount of impurities was found in Ad26.COV2.S. Platelet factor 4 formed complexes with ChAdOx1 nCoV-19 constituents, but not with purified virions from ChAdOx1 nCoV-19 or with Ad26.COV2.S. Vascular hyperpermeability was induced by ChAdOx nCoV-19 but not by Ad26.COV2.S. These differences in impurities together with EDTAinduced capillary leakage might contribute to the higher incidence rate of VITT associated with ChAdOx1 nCoV-19 compared to Ad26.COV2.S.

MeSH terms

Ad26COVS1
COVID-19 Vaccines / adverse effects
COVID-19*
ChAdOx1 nCoV-19
Humans
SARS-CoV-2
Vaccines*

Substances

Ad26COVS1
COVID-19 Vaccines
Vaccines
ChAdOx1 nCoV-19

Grants and funding

Funding: This study was funded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) grants: 374031971 - A06 and A11-TRR240, 398967434 - SFB/TR261, A11 - SFB877, P6 - KFO306, B8 - SFB841, and INST 2026/13-1 FUGG, the Ministerium für Wirtschaft, Arbeit und Gesundheit Mecklenburg- Vorpommern (project COVIDPROTECT), “Structure and Function of the Proteasome System in Platelets“ GR2232/8_1 and SE 885/2-1 (DFG), Leibniz WissenschaftsCampus – ComBioCat – W10/2018, by the Federal Ministry of Education and Research (BMBF, grant 01GM1518B, STOP- FSGS), the Südmeyer fund for kidney and vascular research (“Südmeyer- Stiftung für Nieren- und Gefäßforschung”), the Dr. Gerhard Büchtemann fund, Hamburg, Germany and the PeNe_C19 study by the Ministerium für Wirtschaft, Arbeit und Gesundheit Mecklenburg-Vorpommern.