Quantification of residual plasmid DNA and SV40 promoter-enhancer sequences in Pfizer/BioNTech and Moderna modRNA COVID-19 vaccines from Ontario, Canada https://pubmed.ncbi.nlm.nih.gov/40913… 32 vials representing 16 unique vaccine lots. These data demonstrate the presence of billions to hundreds of billions of DNA molecules per dose in the modRNA COVID-19 products tested. All products tested exceeded the guidelines for residual DNA set by the FDA and WHO of 10ng/dose by 36–627-fold. Total DNA in all vials tested Exceeded the regulatory limit for residual DNA set by the US Food & Drug Administration (FDA) and the World Health Authorization (WHO) by: Pfizer: 36-153-fold Moderna: 112-627-fold 3 Pfizer vials exceeded the regulatory limit for the SV40 promoter-enhancer-ori (p53) The PCR results for the most recent XBB.1.5 Moderna and Pfizer vaccines suggest that DNA residues have not been reduced from previous vaccine versions. Pfizer, Total DNA ranged 371-1,548 ng/dose Moderna, 1,130-6,280 ng/dose Specific DNA of multiple plasmid DNA targets Pfizer ranged 0.22-7.28 ng/dose Moderna 0.01-0.78 ng/dose for Moderna. The SV40 promoter-enhancer-ori(0.25-23.72 ng/dose) was only detected in Pfizer vials. Sequencing of one vial Mean DNA length, 214 bp Maximum length, 3.5 kb Presence of 1.23 × 108 to 1.60 × 1011 plasmid DNA fragments per dose encapsulated in lipid nanoparticles. Our findings extend existing concerns about vaccine safety and call into question the relevance of guidelines conceived before the introduction of efficient transfection using LNPs. This work highlights the need for regulators and industry to adhere to the precautionary principle and provide sufficient and transparent evidence that products are safe and effective, and disclose the details of their composition and method of manufacture. For some of the COVID-19 vaccines, the drug substances released to market were manufactured differently than those used in clinical trials. Rationale for study Manufacturing nucleoside-modified mRNA for commercial COVID-19 vaccines relies on RNA polymerase transcription of a plasmid DNA template. Previous studies identified high levels of plasmid DNA in vials of mRNA vaccines, suggesting that the removal of residual DNA template is problematic. Therefore, we quantified the DNA load in a limited number of Pfizer-BioNTech and Moderna COVID-19 modRNA vaccine vials using two independent methods. This study emphasizes the importance of methodological considerations when quantifying residual plasmid DNA in modRNA products, considering increased LNP transfection efficiency, and cumulative dosing presents significant and unquantified risks to human health.
The association between acute transverse myelitis and COVID-19 vaccination in Korea https://onlinelibrary.wiley.com/doi/1… Acute transverse myelitis (ATM) has been reported as a potential association between COVID-19 vaccination. https://pubmed.ncbi.nlm.nih.gov/38350… Results 368 ATM cases diagnosed after first COVID-19 vaccination during the study period (159 ATM patients were included). Among them, 82 (51.6%) were male The incidence rate ratio (IRR) was 2.41, for the ATM risk within 1–42 days after COVID-19 vaccination. The IRR (Incidence Rate Ratio) 3.31 for ChAdOx1-S (AZ) 1.99 for BNT162b2 (Pfizer) 2.57 for mRNA-1273 (Moderna) 3.33 for Ad26.COV2.S (Janssen) Methods A self-controlled case series study https://www.bmj.com/content/354/bmj.i… Large database that combines the COVID-19 vaccine registry and the national claims database. The COVID-19 vaccination Data, information on individuals aged 18 + who received COVID-19 vaccination from February 26, 2021, to August 31, 2022. Patients who developed acute transverse myelitis The claims database covered the entire Korean population Patients who develop ATM within 1–42 days following COVID-19 vaccination The observation period was 270 days after the first dose of the COVID-19 vaccine. Conclusion These findings indicated an increased risk of ATM following COVID-19 vaccination within 42 days. An association with the risk of ATM was found both for viral vector and mRNA vaccines. Acute transverse myelitis (ATM) A rare neurological disorder Inflammation of the spinal cord Can lead to sensory and motor deficits, paralysis, severe disability, autonomic loss The causes of ATM are uncertain; however, it is known to be associated with autoimmunity triggered by various environmental factors, including vaccination. DISCUSSION This nationwide population-based SCCS study identified a significant increase in the incidence of ATM within 1–42 days following COVID-19 vaccination. Our findings contribute to the ongoing debate on the safety profiles of COVID-19 vaccines by providing evidence of potential neurological complications. An emerging pattern Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection https://onlinelibrary.wiley.com/servl… Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. Acute Transverse Myelitis after COVID-19 Vaccination https://pubmed.ncbi.nlm.nih.gov/34684… The adverse effects of the COVID-19 vaccine have been discovered as the rapid application of the vaccines continues. Neurological complications such as transverse myelitis raise concerns as cases were observed in clinical trials. Overview of Transverse Myelitis after COVID-19 vaccination https://www.lareb.nl/Knowledge/FilePr… Until January 16th 2023, The Netherlands Pharmacovigilance Centre received 48 reports of TM following COVID-19 vaccination. Neurological side effects of SARS-CoV-2 vaccinations https://onlinelibrary.wiley.com/servl… The most frequent neurological side effects of SARS-CoV-2 vaccines are headache, Guillain-Barre syndrome (GBS), venous sinus thrombosis (VST), and transverse myelitis. A systematic review of cases of CNS demyelination following COVID-19 vaccination https://onlinelibrary.wiley.com/servl… Majority of cases (71.8%) occurred after the first dose of the vaccine, with neurological symptoms manifesting after a median of 9 days. The most common reported presentation was transverse myelitis Transverse Myelitis Following SARS-CoV-2 Vaccination: A Pharmacoepidemiological Study in the World Health Organization’s Database https://onlinelibrary.wiley.com/servl… TM was significantly associated both with the messenger ribonucleic acid (mRNA) and vector-based SARS-CoV-2 vaccines that are authorized by the FDA or the EMA.