169. In FOI 2389-3 4.3.3 it says “RNA itself, and the lipids used in the BNT162 vaccines have no carcinogenic or tumorigenic potential. Furthermore, according to ICH SIA, no carcinogenicity studies are required for therapeutics that are not continuously administered. Therefore, no carcinogenicity studies were performed.’ Why is carcinogenicity not tested if boosters are being continually rolled out? 170. In FOI 2389-3 5.3.1.7 regarding coagulation it says “Increases in fibrinogen levels were detected in all vaccinated animals at the end of dosing phase and were consistent with an acute phase response secondary to immune activation and inflammation at the injection sites.” Given clotting was a recognised side effect of the vaccine on what basis can the TGA rule out strokes and other clotting related events? 249. What is the different 5 cap structure in modified RNA – page 109 FOI 2389-3 – how is this different to the Covid spike protein mRNA cap? 250. FOI 2389-3 page 20 – some LNPs can be twice as big as others 60-120 nano metres Does this mean that some vaccine lipids can be twice as toxic or efficacious, or some people will get twice the dose of others? 251. In the Pfizer Covid vaccine as per FOI 2389-3 page 110 Table 2 – Theorical length is from 1200 to 4500 nucleotides depending on selected antigen – the Coronavirus spike protein has 1273 amino acids – why is the vaccine producing a spike protein almost 4 times larger than the Covid virus?

Question Number: 247
PDR Number: SQ22-000617
Date Submitted: 21/11/2022
Department or Body: Department of Health

Question 169 Carcinogenicity studies are generally not required under international (ICH) protocols for pharmaceuticals that are administered to patients infrequently (e.g. a few doses per year) or for vaccines or biological medicines. Question 170 Nonclinical studies with the COVID-19 vaccines in laboratory animal species do not indicate potential for causing blood coagulation. Nonclinical toxicology studies were conducted with a single dose or repeated doses of the COVID-19 vaccine in its final clinical formulation as administered to patients. Vaccine doses in the nonclinical studies were very high, up to 200-times the human dose (vaccine dose per kg body weight). These studies did not show any effects of the vaccines on platelets and coagulation parameters (i.e., platelet count/volume/distribution width, prothrombin time, activated partial thromboplastin time) or development of blood clots. The Therapeutic Goods Administration (TGA) continues to monitor national and international data on the risk of blood clots with COVID-19 vaccination. The TGA has not identified a causal link between mRNA vaccines and the formation of blood clots Question 249 mRNA in the Pfizer COVID-19 vaccine is capped at the 5’ end using a trinucleotide cap 1 analogue ((m2 7,3?-O)Gppp(m2?-O)ApG) (available at: https://pubmed.ncbi.nlm.nih.gov/32998157/). The SARS-CoV-2 genome, like all other hCoVs, such as SARS-CoV and MERS-CoV, has a m7G-cap structure, m7GpppA1, on the 5? end (available at: https://pubmed.ncbi.nlm.nih.gov/34281608/). 5? capping of mRNA is important in mRNA stability and efficient translation to protein. The slight difference between the 5’ capping of the vaccine mRNA and viral genome capping has no impact on the structure and properties of spike protein synthesised from the mRNA. Question 250 Lipid nanoparticles (LNPs) used in COVID-19 vaccines and other pharmaceutical products (e.g. ONPATTRO, a short interfering RNA drug product approved in the USA and EU) are present in a range of sizes depending on the product and the size of the mRNA for example. The biological effect of LNPs of different sizes may differ, but efficacy and safety of the approved COVID-19 mRNA vaccines with LNPs in the specified size range have been demonstrated in nonclinical studies, clinical trials and clinical use. The dose for COVID vaccines is based on antigen and LNP weight and contains a consistent amount of mRNA and LNPs. Question 251 The single-stranded mRNA in COMIRNATY encodes the spike protein of SARS-CoV-2. The reason the theoretical length of the vaccine is larger than the COVID virus is that the sequence of the mRNA was optimized with changes, which does not form a part of the spike protein, to enhance stability and translation efficiency of the vaccine.