‘You don’t need a biologist on board to make these, you need a chemist’
With Covid-19 vaccines widely available, the scientist behind experimental technology used by pharmaceutical companies Pfizer and Moderna has explained what was baked into the first batch off the production line.
Dr Drew Weissman, a professor in the University of Pennsylvania’s Perelman School of Medicine, is one of the pioneers of the vaccine formula called Messenger RNA (mRNA). He collaborated with Pfizer and BioNTech on their version of the vaccine.
He told The Independent that the vaccine, unlike any that has been developed previously, contains a new technology that delivers genetic code – or directions – that instructs the body to create a copy of the Covid-19 virus “spike” protein, which prompts an immune response.
“The mRNA is produced by an enzyme that copies DNA that contains the protein to be produced,” Mr Weissman said.
“Four lipids are used to create the lipid nanoparticle that self-assemble with the mRNA. They are all created synthetically. The cationic lipid, which is the main function component is proprietary to companies.”
Dr Weissman explains the Covid-19 vaccines contain only the synthetically created mRNA genetic code and four lipids, known as lipid nanoparticles, in contrast to traditional vaccines that are created within living cells and contain components of a virus.
“None of this is made in mammalian cell lines,” he said.
The result is a 95 per cent effective vaccine, according to Pfizer and BioNTech, while Moderna says its version is 94.5 per cent effective.
Traditional vaccines contain an active component to generate an immune response, usually tiny fragments of the disease-causing organism in the form of a protein, as outlined by the World Health Organization.
They also contain preservatives like 2-phenoxyethanol and stabilisers like sugars (lactose, sucrose), amino acids (glycine), gelatin, or proteins (recombinant human albumin, derived from yeast).
Surfactants, used in foods like ice cream, keep the ingredients together while residuals from the manufacturing process, like egg proteins, yeast or antibiotics, can be found in trace amounts.
They also use diluents like sterile water and adjuvant stimulate local immune cells, which can be aluminium salts like aluminium phosphate, aluminium hydroxide or potassium aluminium sulphate.
The experimental vaccines from Pfizer and Moderna, technically called BNT162b2 and mRNA-1273, respectively, are created synthetically using messenger Ribonucleic acid (or mRNA). RNA and DNA (Deoxyribonucleic) are nucleic acids that carry genetic instructions for creating life.
Rather than injecting an organic version of the virus to generate an immune response, mRNA contains snippets of the coronavirus spike protein’s genetic code that tells the body’s cells to produce a small facsimile of that spike protein, which kickstarts the immune system to produce antibodies.
“This is done with the DNA that has a sequence that binds the enzyme and tells it to start working, followed by the sequence of the protein. There are other sequences that increase the amount and duration of protein production,” Dr Weissman said.
“Our mRNA vaccine differs as one of the nucleotides, letters, is modified and that gets rid of the inflammatory potential of the mRNA.”
Paula Cannon, an associate professor of microbiology at the University of Southern California’s Keck School of Medicine, told The Independent that vaccine’s developers have improved on natural RNA, which are short-lived and fragile.
“They can be made entirely synthetically, you don’t need a biologist on board to make these you need a chemist,” Ms Cannon said.
“Part of the secret source of these vaccines is that the chemists have found a way to modify RNA and improve on what nature has developed to increase its stability and damp down its foreignness to the body. We don’t want the body to freak out about this RNA that’s been injected into it. So there’s been some chemical modifications to make the RNA a bit more stealthy.”
The closest glimpse of what, exactly, those chemists put into the Covid vaccine came in the FDA’s emergency use authorisations breaking down the ingredients in Pfizer’s BNT162b2 and Moderna’s mRNA-1273. Brace for medical jargon.
In the Pfizer vaccine, mRNA is delivered by the four lipids: “((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-Distearoyl-sn-glycero-3-phosphocholine, and cholesterol)”.
To balance acidity in the body, the vaccine includes the salts potassium chloride, monobasic potassium phosphate, sodium chloride, and dibasic sodium phosphate dihydrate. Basic table sugar, or sucrose, is included to help molecules maintain shape while frozen.
The Moderna vaccine is similar but has slight differences in the delivery of the mRNA. The lipids used include: “(SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC])”.
To balance acidity it uses acetic acid, Tromethamine & Tromethamine hydrochloride, and sodium acetate. Sucrose is also used to maintain form.
(Separately, the Johnson & Johnson vaccine that uses a different DNA technology is delivered using a modified version of a different virus, Adenovirus 26, that was first isolated in 1956 from an anal specimen of a 9-month-old male child. It also includes citric acid monohydrate, the salt trisodium citrate dihydrate, the sugars 2-hydroxypropyl-β-cyclodextrin (HBCD) and polysorbate-80, sodium chloride, as well as ethanol.)
“It’s like a carrier and protective chemical that helps to package up and protect and help with the delivery of the RNA. That’s often based on lipids made entirely chemically,” Ms Cannon said.
“So you have one flask that’s making the RNA and one flask that’s making the lipid, and they get kind of mixed together and the way that the chemistry is designed is that the RNA is attracted to the lipid, it forms a complex with it, and that puts the RNA in a Goldilocks spot.”
For Pfizer’s vaccine, it needs to be stored at a temperature of at -94 F to remain in that Goldilocks zone, while Moderna’s vaccine needs to stay at -4 F.
Researchers have been attempting to trick the body’s immune system using mRNA for decades, and the Covid vaccines are the first successful implementation since research began in the early 1990s. The experimental technology not only makes an impact on the Covid pandemic, but it also opens the door to a whole line of vaccines for viruses like Herpes, HIV and the Flu.