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

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 ChAdOx1 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson). ChAdOx1 nCoV-19 contains significant amounts of host cell protein impurities, including functionally active proteasomes, and adenoviral proteins. In Ad26.COV2.S a much lower amount of impurities was found. Platelet factor 4 (PF4) 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 EDTA-induced capillary leakage might contribute to the higher incidence rate of VITT associated with ChAdOx1 nCoV-19 compared to Ad26.COV2.S.

Anti‐severe acute respiratory syndrome coronavirus‐2 adenoviral‐vector vaccines trigger subclinical antiplatelet autoimmunity and increase of soluble platelet activation markers

“…EVs, extracellular vesicles adenoviral proteins, present in significant amounts in the ChAdOx1 vaccine preparation. [46][47][48] Moreover the adenoviral-vector of COVID-19 vaccines itself, leaking in the circulation, may bind coxsackie and adenovirus (Ad) receptor (CAR) or arginine-glycine-aspartate (RGD)containing integrins on the platelet surface, thus activating them. 4 The presence of CAR on platelets is still debated.…”

A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA Vaccination against Covid-19

“…In phase III clinical trial of the ChAdOx1-nCov-19 vector vaccine, a few cases of transverse myelitis were reported (O'Reilly, 2020; Voysey et al, 2021). Moreover, Serious neurological disorders were reported following different mRNA-based vaccination including transverse myelitis, Guillain-Barré syndrome, cranial nerve neuropathies, myelitis, and facial nerve palsy (García-Grimshaw et al, 2021;Lau & Galea, 2022;Malhotra et al, 2021;Michalik et al, 2022;Wan et al, 2022). A study reviewing case reports and case series reported the occurrence of variable central and peripheral nervous system complications in patients receiving gene-based vaccines including transverse myelitis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis (Sriwastava et al, 2022).…”

“…The emergency-based WHO policy authorized the entry of the "operation warp speed" mRNA-based vaccines that were approved by the emergency use authorization by the US Food and Drug Administration after only one year of development. Although the published phase 3 clinical trials reported fewer side effects and minor non-fatal complications (Baden et al, 2021;O'Reilly, 2020;Sultana et al, 2020)b, the accumulating evidence of serious neurological (Michalik et al, 2022(Michalik et al, , 2022; S. J. Thomas et al, 2021;Wan et al, 2022) and cardiac complications (Cari et al, 2021;Dionne et al, 2021;Jabagi et al, 2022) as well as death reports (Torjesen, 2021) shortly after receiving the first (García-Grimshaw et al, 2021) and the second doses of mRNA-based vaccines casts heavy shades of doubt on the safety profile as well as the preclinical studies of such types of vaccines (European Medicines Agency (EMA), 2021).…”

“…Subsequently, the diverse effects of COVID-19 vaccines after market introduction have attracted attention for further assessment and investigation (Michalik et al, 2022). The challenge emerged that continuous and extensive monitoring of the vaccine's safety profile should be underscored.…”

Potential mechanisms of vaccine-induced thrombosis

“…The induction of the anti-PF4 immune response requires a proinflammatory milieu, which can be elicited by several vaccine components, such as human cell line proteins, free virus proteins, EDTA and AdV genetic material. Relevant to this, a higher proportion of host-cell proteins, active proteases and unassembled hexon proteins has been found in the ChAdOx1 nCoV-19 vaccine as compared to the Ad26.COV2.S [45] . This finding suggests that a different intensity of the inflammatory response elicited by different AdV vaccines can play a role in the production of the functionally active PF4 antibodies involved in the development of VITT.…”