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QUESTION ON NOTICE

Question:

21 November 2022

89. In the TGA non-clinical report it states “the S protein is synthesised and processed within the ER for surface expression or secretion.” Why is the vaccine stimulating the human body to export the spike protein from the cell – shouldn’t it be sterilising the virus rather than reproducing it? 90. What impact does the secretion of spike proteins have on the endothelium and other sensitive body organs? 91. Has the TGA done any research on the secretion of proteins from the cell as a result of the vaccine? If not, why not? 92. What evidence does the TGA have to prove that proteins secreted from the cells don’t cause clots and damage to body organs? 93. How does the TGA know that the ribosome translates the mRNA code 100% accurately and no mutations occur if no mutagenic studies have been done? 94. Has the TGA done any distribution and degradation studies to determine the potential toxicity of the secreted spike protein. If not, why not?

Answer:

Question Number: 185
PDR Number: SQ22-000555
Date Submitted: 21/11/2022
Department or Body: Department of Health

Question 89 The expressed spike protein in vitro (in HEK293 cells) co-localised with an endoplasmic reticulum (ER) marker, suggesting the S protein is synthesised and processed within the ER for surface expression. This study did not show that the vaccine stimulates the human body to export the spike protein from the cell. The spike protein has a transmembrane anchor region that makes the protein attach to the cell membrane, and hence it is not secreted or released into the blood stream from the cells due to the absence of a signal sequence for secretion (available at: www.pubmed.ncbi.nlm.nih.gov/33117378 and www.pubmed.ncbi.nlm.nih.gov/34400651/). The spike protein in mRNA vaccines is stabilised to prevent the protein from splitting into smaller units and shedding. Put simply, the spike protein is assembled from mRNA and processed by machinery inside a cell. A specific region (transmembrane anchor region) of the spike protein gives a signal to the cells for the spike protein to be transported and attached to the cell membrane. The spike protein expressed on the cell surface is recognised by the immune cells as foreign and generates an immune response to defend against SARS-CoV-2 infection (available at: www.pubmed.ncbi.nlm.nih.gov/34211186). Most importantly, the spike protein is not a pathogen. The spike protein is only one component of the coronavirus. It serves as an antigen to induce immune responses with subsequent minor local inflammatory effects. Also, vaccines do not reproduce viruses.

Question 90 The spike protein synthesised from the vaccine mRNA is not secreted. Vaccines mostly remain near the site of injection, e.g. the arm muscle, and are also distributed to local lymph nodes, liver and spleen. There is no evidence of endothelium damage following vaccination. Nonclinical toxicity studies in animal species with high doses of the vaccine showed no damage to any organs except for inflammation at the injection site.

Question 91 See answer provided to question 90.

Question 92 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. These studies, conducted in animals (rodents, ferrets, hamsters, non-human primates) have not shown any adverse effects, including changes in platelets and coagulation parameters (i.e. platelet count/volume/distribution width, prothrombin time, activated partial thromboplastin time or the development of blood clots, following immunisation with COVID-19 vaccines at doses up to 200-times the human dose (vaccine dose per kg body weight). The findings in the animal toxicology studies were consistent with known immune responses, including inflammation at the injection site.

Question 93 There is no evidence of mutation of vaccine mRNA. The presence of vaccine mRNA in the cell is transient, and the vaccine mRNA in the Pfizer and Moderna vaccines is non-replicating. The mRNA is quickly metabolised and eliminated via normal cellular processing mechanisms. The vaccine mRNA is expected to be degraded by multiple pathways (e.g. deadenylation, endonuclease-mediated decay), while the antigen protein undergoes proteolysis as for endogenous proteins. Unprotected mRNA (once released from the lipid nanoparticle carrier) is destroyed within minutes in biological fluids and does not persist in tissues. Therefore, no mutagenic studies were conducted by the vaccine manufacturers, nor did major regulators require these to be done based on this scientific background.

Question 94 There were no distribution or degradation data on the spike antigen-encoding mRNA or expressed spike protein. Following the administration of lipid nanoparticles (LNP) encapsulating mRNA vaccines to mice, the LNPs encapsulating mRNA were mainly located around the injection site with a small amount distributing to other tissues and organs. The mRNA is expected to go to muscle cells and other types of cells at the injection site, where spike protein is synthesised. A whole-body imaging study in mice with a surrogate luciferase expressing mRNA indicated that the mRNA and translated spike protein were mainly localised at the injection site and to a lesser extent in liver, and nearly completely degraded in nine days. Spike protein expression was detected in antigen presenting cells in draining lymph nodes and spleen in mice after injection of the Moderna mRNA vaccine. Thus, the spike protein is expected to be mainly expressed at the local injection site, liver, draining lymph nodes and spleen. The spike protein expressed at distant sites in other organs would be extremely low and short lived (hours to several days). The Infectious Disease Society of America estimated that the spike proteins that were generated by COVID-19 vaccines would last up to a few weeks, like other proteins made by the body (available at: www.idsociety.org/globalassets/idsa/public-health/covid-19/realtime-learning-network-vaccines-faq.pdf, p12). In a recent publication of a small human study, vanishingly low levels (in picograms/mL) of a fragment of the spike protein were detected in plasma of 11 out of 13 human subjects from one day to nine days after the first injection, and the full-length spike protein in three out of 13 subjects from days nine to 29. The disappearance of the fragment and spike proteins was associated with induction of anti-S1 fragment and anti-spike antibodies. After the second vaccine dose, no S1 fragment or full-length spike protein was detected (available at: https://academic.oup.com/cid/article/74/4/715/6279075). There is no scientific evidence indicating that the spike protein created in our bodies from the COVID-19 vaccines is toxic or damaging, and hence no further studies have been requested.