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QUESTION ON NOTICE

Question:

24 February 2022

233. Can the TGA or Pfizer show studies that all of the mRNA gets taken up by the cells? 234. What happens to the lipid nanoparticles that don’t get taken up by the cells? 235. How long will a spike protein produced by the mRNA vaccine stay in the body? 236. For the mRNA/Lipid Nanoparticles that doesn’t get taken up by cells is there a risk they mutate and become toxic in the body? 237. If the genetic Covid-19 vaccine is damaged in handling or storage how does Pfizer/TGA know that the mRNA won’t produce mutations of the spike protein rather than the protein itself? 238. After the Covid vaccine is given how quickly will the body start to produce spike proteins and how quickly after that will the body start to produce antibodies? 246. What cells or organs is the mRNA code meant to go into – just muscle cells or other organ cells as well – has this been tested – how can the TGA guarantee that Lipid nanoparticles or spike proteins won’t go into other organs?

Answer:

Question Number: 197
PDR Number: SQ22-000177
Date Submitted: 24/02/2022
Department or Body: Department of Health

233. The percentage of the mRNAs that are taken up by the cells is not determined, but the amount entering the cell is sufficient to produce enough spike protein for the induction of adequate immunity against SARS-CoV-2 infection. The cells make copies of the spike protein and the mRNA is quickly degraded (within a few days). Unprotected mRNA (once released from the lipid nanoparticle carrier) is destroyed within minutes in biological fluids and is unlikely to persist in tissues or in the bloodstream.

234. Lipid nanoparticles are tiny lipid droplets that transport the mRNA to cells and protect the vaccine mRNA. Owing to their size and properties, lipid nanoparticles are taken up by cells via endocytosis. Lipid nanoparticles are broken down just like any other lipids in the human body.

See also response to Q 246 below.

235. There are no distribution and degradation data on the S antigen-encoding mRNA or expressed spike protein. A whole-body imaging study with a surrogate, luciferase expressing mRNA in mice indicates that the mRNA and translated antigen protein are nearly completely degraded in 9 days. The Infectious Disease Society of America estimates that the spike proteins that were generated by COVID-19 vaccines last up to a few weeks, like other proteins made by the body. The immune system quickly identifies, attacks and destroys the spike protein because it recognizes it as foreign.

236. No. There is no evidence of mutation of vaccine or therapeutic mRNA. The presence of vaccine mRNA in the cell is transient, not permanent, and the vaccine mRNA 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, 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 is unlikely to persist in tissues.

See responses to Q 234 and Q 246 regarding distribution, degradation and safety of lipid nanoparticles.

237. All shipments of the Pfizer COVID-19 vaccine COMIRNATY are temperature monitored and handling logged. As part of the quality requirements, the Sponsor must inform the TGA of any temperature deviation during shipment and not supply product that has been exposed to a temperature excursion outside of the approved storage conditions. Additionally, TGA undertakes laboratory testing on arrival in Australia of every batch of COMIRNATY vaccine, as part of the batch release assessment process, which includes testing for RNA integrity. The specification limits set for these tests have been established as safe during the clinical development of the vaccine.

238. Following vaccination, the mRNA will enter human host cells and instruct the cells’ machinery to produce the spike protein. It was not determined how quickly this happens; however, this process happens using host cells’ machinery in a natural way. After the spike protein is made, host cells break down the mRNA and remove it. Next, host cells display the spike protein on their surface. The host immune system recognises that the protein doesn’t belong there. This triggers the immune system to produce antibodies and activates other immune cells to fight off an infection.

The humoral and cellular immune response following intramuscular administration of COVID-19 mRNA vaccines was investigated in nonclinical studies in animals and in clinical trials. Following mRNA vaccine administration, anti-spike protein antibody titres in blood peak around two to three weeks after injection. It typically takes a few weeks after vaccination for the body to produce memory T cells.

246. Following the administration of lipid nanoparticles (LNP) encapsulating mRNA vaccines to mice, the LNPs encapsulating mRNA are mainly located around the injection site with a small amount distributing to other tissues and organs. mRNA is expected to go to muscle cells and other types of cells. A whole body imaging study in mice with a surrogate, luciferase expressing mRNA indicates that the mRNA and translated spike protein are mainly localised at the injection site and to a lesser extent in liver, and nearly completely degraded in nine days.

Thus, the spike protein is expected to be mainly expressed at the local injection site and liver. The spike protein expressed at distant sites in other organs would be extremely low and are relatively short lived (hours to several days). Moreover, unprotected mRNA (once released from the lipid nanoparticle carrier) is destroyed within minutes in biological fluids and is unlikely to persist in tissues.