Extract from ABC News
More than 100 million people across 66 countries have received at least one COVID-19 jab, and all in just a few short months.
Not only were these vaccines developed and tested at blistering pace — less than a year — but they're also being produced on a mass scale.
So how are they made?
Some production details are trade secrets.
But we do know that the three vaccine technologies we're likely to get in Australia don't incorporate, or even handle, the actual virus that causes COVID-19.
They instead use genetic instructions for a very specific part of the SARS-CoV-2 virus, the spike protein, which the virus uses to hook onto and infect our cells.
And while they all grow (or culture) cells and microbes in bioreactors as part of their production, they all do it differently.
Growing spike protein antigens
The most conventional style of vaccine is the protein subunit vaccine. The Novavax jab, as well as most of the jabs we get in childhood, fall under this umbrella.
These vaccines stimulate an immune response by directly delivering bits of the virus they're designed to protect us against.
There are a few ways to make these bits, called antigens, but they all generally involve cell lines: populations of cells living in a soup of nutrients and other essential compounds.
A commonly used cell line in mass antigen production are Chinese hamster ovary or CHO cells, which are pretty hardy little things: they can put up with swings in temperature, pH and oxygen levels.
The cells can also make and churn out loads of a specific molecule, such as the SARS-CoV-2 spike protein, if given the genetic instructions to do so.
(No hamsters were harmed in the making of the vaccine. This cell line and others used in vaccine production were descendants from cells isolated from an animal years, perhaps even decades, ago.)
CSIRO's Melbourne biologics production facility scaled up the spike protein antigens used in the University of Queensland's vaccine clinical trials last year, says Susie Nilsson, Biology Group Leader at CSIRO Biomedical Manufacturing and a lab head at the Australia Regenerative Medicine Institute.
The engineered CHO cells are grown inside bioreactors. Batches of cells are bagged separately to avoid contamination.
Novavax production forgoes CHO cells; rather, it employs cell lines extracted from moths to manufacture its spike protein antigens.
The moth cells get their instructions to generate antigens from a virus that only infects insects.
mRNA wrapped in a greasy sheath
The newest style of vaccine are mRNA vaccines, such as those developed by Pfizer/BioNTech and Moderna.
These are fairly basic in structure, with just a strand of genetic material — that's the mRNA or messenger RNA — encapsulated in a protective envelope.
The message carried by the mRNA is a blueprint for our cells to construct copies of the SARS-CoV-2 spike protein, which we then use to train our immune system to recognise in case it sees the real thing down the track.
To make these vaccines, you first need a DNA template to make the mRNA, says Magdalena Plebanski, a professor of immunology at RMIT University.
"You can synthesise DNA fully artificially, but it's a real pain," she says.
"It's the quickest, cheapest and easiest way of doing it."
Once you have your DNA templates, they're incubated in a cocktail of mRNA building blocks and enzymes.
The enzymes follow the template to construct mRNA strands.
Because mRNA strands tend to fall apart easily, they need to be protected in a fat-rich sheath called a lipid monoparticle.
To safely ensconce the mRNA in its protective monoparticle, they're shot at each other in a process called impingement jet mixing.
"Everything swirls around in the jet mixer and they create nanoparticles," Professor Plebanski says.
Genes housed in a virus
The Oxford/AstraZeneca and Johnson & Johnson vaccines use a different type of virus, an adenovirus, to protect us against SARS-CoV-2.
These adenoviruses don't make us sick, but contain the genetic blueprint for the SARS-CoV-2 spike protein.
But unlike mRNA vaccines, where the instructions are in the form of a long, fragile single-stranded molecule, genetic instructions in adenovirus vaccines form part of a ring of double-stranded DNA.
This makes them much more stable than mRNA vaccines, and is why they can be stored at normal fridge temperatures.
It almost sounds counterintuitive to deliberately use a virus in a vaccine.
But scientists can harness a virus's ability to efficiently deliver genes into cells, while removing parts of its genome to ensure it can't replicate in a vaccinated person's cells.
Instead, it carries the spike protein DNA instructions into the cell, where the genes are "read" and transcribed into mRNA.
From there, it's the same process as the mRNA vaccines.
The DNA in the vaccine does not get incorporated into your own DNA, either. After a time, the DNA ring is dismantled and destroyed by the cell's natural waste disposal processes.
And making adenovirus-based vaccines is relatively straightforward once you have a sample of the vaccine, Professor Plebanksi says.
The process also uses cells living and growing in bioreactors, but instead of CHO cells, adenovirus vaccine production enlists the help of a particular cell line dubbed HEK 293.
Even though HEK 293 cells originally came from a human — a kidney, back in 1973 — they are engineered to allow vaccine adenoviruses to replicate inside them.
"So you take a sample of your adenovirus vaccine, you infect your cells, and you let them grow," Professor Plebanski says.
Purifying and packaging
At various stages of the production process, vaccines and their components must be filtered.
This not only ensures the product is pure, but also sterile.
First, they spin the solution to get rid of the chunks, namely the cells in which the vaccine components grow.
The remaining liquid is then usually sent trickling through special membranes or resin columns in a process called chromatography, which separates components from the soup.
Then it's simply a matter of collecting the pure product from the resin or membranes.
Before packaging, vaccines are mixed with a buffer solution — often saline — and sometimes other compounds such as adjuvants, which help "wake up" your immune system and elicit a stronger response.
They're then packaged into vials and shipped off to where they're needed. But this is a whole other story.
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