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 much less impurities were 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.

Cardiovascular, neurological, and pulmonary events following vaccination with the BNT162b2, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines: An analysis of European data

“…As far as we know, the differences between the vaccines are as follows: 1) The type of adenovirus is different (human Ad26 and chimpanzee adenovirus in the AD26 and ChA vaccines, respectively); 2) the human cell lines by which adenovirus are produced are different: T-REx-293 cells for ChA and PER.C6 TetR cells for AD26 [ 44 ]; 3) ChA contains a large number of host cell proteins differently from AD26 [ 10 , 44 , 45 ]; 4) chimpanzee adenovirus has a stronger negative charge than human AD26 [ 40 ]. Molecular simulations suggest that the chimpanzee adenovirus charge, combined with aspects of the virus shape, could allow it to bind to the positively charged PF4 protein [ 46 ]; 5) The number of viral particle in the AD26 vaccine is 3.3-fold higher than that in the ChA vaccine [ 47 , 48 ], possibly implying a higher spike protein and adenoviral protein burden.…”

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.…”

Nucleic Acid Sequence Composition of the Oxford – AstraZeneca Vaccine ChAdOx1 nCoV-19 (AZD1222, Vaxzevria)

“…Research into the causes is ongoing. Preliminary ndings hint that residual host cell protein in the vaccine solution, and the physical vaccine structure may contribute (5,6). Secretion of soluble spike protein from incorrectly spliced spike transcripts was also recently proposed as an adverse factor in VITT development (7).…”