Maryanne Demasi | 15 Feb 2022

Spike proteins on the surface of the SARS-CoV-2 virus are responsible for the pathogenesis of COVID-19.

There is a concern however, that spike protein in the body after vaccination is “toxic.”

To address these concerns, I spoke with vaccine developer, Professor Nikolai Petrovsky from Flinders University in South Australia. He has developed a protein-based vaccine called COVAX-19 (or Spikogen) which has received emergency use authorisation in Iran. 

He says that the spike protein in protein-based vaccines (Novavax/COVAX-19) is markedly different from that generated by gene-based vaccines (Pfizer/Moderna/AZ).

Is spike protein “toxic”?

“Having had multiple doses of a spike protein vaccine myself, I don’t believe it is intrinsically toxic. We’ve put spike protein onto human cells in the lab and the cells don’t die or do anything strange. If you put a true toxin on cells, they die quickly, whereas spike protein doesn’t have any obvious ‘toxin’ effects that we can see,” said Prof Petrovsky. 

“Before giving it to humans, we injected extremely large doses into mice but didn’t see any adverse effects. This was very reassuring. A real toxin like tetanus toxin, is lethal even at miniscule amounts. So, spike protein is clearly not a toxin in the true sense of the word,” he added.

In fact, injecting purified spike protein is biologically ‘inert’ he said, which is why it must be combined with an “adjuvant.”

“When we injected spike protein only into mice, we didn’t get a strong immune response – it largely got ignored by the immune system. We added our sugar-based adjuvant to the spike protein to tell the immune system to respond to the protein by making protective antibodies and T-cells against it.  This is why protein-based vaccines are generally safe. When the body confronts most proteins, even foreign ones, it will often regard them as harmless and not make much effort to react to them and make antibodies but rather just metabolises the foreign protein down into its amino acid parts.”

But what about gene-based vaccines – does the spike protein generated by these vaccines have a different effect on the immune system? 

Yes, is the simple answer.

Protein based vaccines inject a fixed amount of spike protein intramuscularly, which remains outside cells

The purified spike protein does not enter inside muscle cells at the injection site – it remains extracellular.

“It stays outside of the cells, and it’s presented to memory B cells [which morph into plasma cells] and they start making antibodies. Special cells called macrophages, which are the garbage collectors of the immune system, sweep up all the proteins outside the cells and break them down. Therefore, it’s very unlikely to have a toxic effect, because it’s not getting inside your other cells,” said Prof Petrovsky.

“The macrophages that eat it up, keep the spike protein in little rubbish bags called phagosomes so the spike protein is not able to float freely inside those cells where it could interfere in their machinery” he added.

Conversely, the spike protein generated by cells from gene-based vaccines interaction with the immune system in a very different way.

Gene-based vaccines result in an unregulated amount of spike protein being manufactured inside cells throughout the body, not just specialised immune cells.

The mRNA molecules have been deliberately manipulated to become more stable once inside the cell. A “pseudouridine” molecule has been added to the mRNA to give it a longer half-life than normal mRNA. Therefore, the production of spike protein within the cell is not being turned off. The implications of this are not well understood.

A recent study published in the journal Cell, showed that vaccine-derived spike protein and mRNA persist for up to two months in the germinal centres of lymph nodes.

While it is said that the mRNA does not enter the cell’s nucleus, and does not interact with your DNA, Prof Petrovsky is concerned that the spike protein being manufactured in the cell may impact cellular function. 

“With the genetic vaccines, the spike protein is being manufactured inside cells (in the cytoplasm) and the amount of spike protein being made is unknown. This spike protein may interfere with normal cellular functions and also may go to the nucleus. After all this is what the virus itself does, which is to express spike protein inside your cells as part of its takeover of your cellular machinery,” he said.

In support of this thesis, researchers published a study where they used a laboratory cell line to show that spike protein “significantly inhibits DNA damage repair.”

“In addition to potentially interfering with cellular functions, including blocking important anti-viral defenses such as interferons, the spike protein will also be presented on the surface of that cell, where it will be recognised and attacked by killer T-cells, potentially resulting in death of the spike protein-expressing cells,” said Prof Petrovsky.

In fact, spike protein can be excreted from the cells and finds its way into the blood stream. A small study showed that spike protein could be detected in the blood of 11 of the 13 participants following vaccination with Moderna’s mRNA vaccine.

Most concerning is regulatory data of Pfizer’s own biodistribution studies (see table)

The data shows that mRNA-lipid nanoparticles do not stay locally at the injection site as first proposed, but can circulate and deposit in various tissues and organs.

Animal studies show mRNA-lipid nanoparticles can deposit in the adrenal glands, liver, ovaries and spleen. It may also cross the blood-brain-barrier and deposit in the brain because of its lipid compatibility, which concerns Prof Petrovsky.

This could not happen with the spike protein from protein-based vaccines, because the proteins are too large to cross the blood-brain barrier. 

The long term significance of the accumulation of mRNA-lipid nanoparticles in various organs, especially after repeated boosters, remains unknown.