Question Number: 189
PDR Number: SQ22-000133
Date Submitted: 24/02/2022
Department or Body: Department of Health
Question 128
There is no evidence that the Pfizer COVID-19 mRNA vaccine COMIRNATY contains MicroRNAs (miRNA) or oncogenic miRNA. miRNAs are short RNAs of around 22 nucleotides. They exist naturally in animals and humans, and thousands of miRNA genes have been discovered in humans. The main function of miRNA is to downregulate gene expression by translational repression, mRNA cleavage and deadenylation. There is no evidence of a positive association of miRNA with adverse effects of COVID-19 vaccination.
Questions 129 & 130
The developers of Covid mRNA vaccines analysed the products of translation of the artificial mRNAs very carefully. They have introduced multiple stop codons in the vaccines to prevent readthrough of the termination codon. The COMIRNATY vaccine consisted of N1-methyl-pseudouridine (Ψ) modified (N1-methyl-Ψ) mRNA encoding the SARS-COVID-19 Spike protein featuring two consecutive UGA stop codons. These were included to minimise the risk the vaccine uses consecutive stop codons as a fail-safe mechanism, so that no frameshifting occurs when the first stop codon fails given an additional in-frame stop codon is expected to prevent the production of unintended proteins.
Pseudouridine has been used in the development of mRNA therapeutics including mRNA vaccines for many years with an aim to enhance RNA stability, antigen expression and adaptive immune responses and to reduce cytotoxicity of modified mRNA. For identical reasons, pseudouridine was used in the COMIRNATY mRNA vaccine to ensure translation efficiency, stability and safety of the vaccine. It has also been reported that N1-Methyl-Pseudouridine-modified mRNA exhibits higher efficacy as compared to the unmodified mRNA vaccines encoding the SARS-COVID-19 spike protein.
The probability of misreading of the vaccine mRNA is very low. Any unintended protein that might be produced would be eliminated from the body. Repeat dose toxicity studies in animal species with the vaccine at doses many times the human dose have indicated no vaccine-related safety risks except for local inflammatory reactions.
Question 131
The Therapeutic Goods Administration (TGA) undertakes laboratory testing on every batch of COVID vaccine, including mRNA vaccines, as part of the batch release assessment process. This includes testing for RNA integrity and identity which involves quantifying the amount of RNA ‘strands’ that are of correct length and sequence to be made into spike protein. A minimum amount of full-length RNA must be present in each batch to pass this test, additionally, the amount of fragment forms of RNA must be below a set specification. The specification limits set for these tests have been established as safe during the clinical development of the vaccine.
Question 132
The mRNA sequence in the mRNA vaccine encodes the spike protein only. There is no evidence of proteins, other than the spike protein being expressed from the vaccine mRNA.
See also response to Q129.
Question 133
Contained in the final vaccine product is the drug substance/active ingredient [mRNA], which is a synthesized, single-stranded, 5′-capped RNA based on the DNA sequence template (www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html and www.ncbi.nlm.nih.gov/pmc/articles/PMC8110223/pdf/jocmr-13-204.pdf). The amount of mRNA per dose is measured in weight rather than strands of mRNA. Each dose of COMIRNATY contains:
• 12 years and over: 30 μg of RNA in 0.3 mL.
• 5 to under 12 years: 10 μg of RNA in 0.2 mL.
Question 134
Each vaccine multi-dose vial contains an overfill to ensure that there is at least one to 1.5 extra doses in the vial to ensure that the end user is able to withdraw the appropriate amount for each dose.
