Editor’s be aware: Anne Moore is a senior lecturer in biochemistry and cell biology at College School Cork and a specialist in vaccine growth. We spoke to her for episode three of The Dialog Weekly podcast on vaccine manufacturing.
Beneath are excerpts from our dialog which were edited for size and readability.
First, are all of the vaccines the identical?
No. Totally different COVID-19 vaccines use totally different applied sciences, or “platforms”. Probably the most standard one is the inactivated vaccine. It comprises lifeless virus. As a result of the virus remains to be complete, it has the entire components, within the right form, that may stimulate a response from the immune system – what we name the antigens. The immune response will be towards a number of antigens.
The Chinese language vaccines – from Sinovac and Sinopharm – are the primary ones utilizing this platform. It’s a terrific expertise, it really works for some human and veterinary vaccines. The identical strategy was used for seasonal flu vaccines some years in the past.
Then there are the viral-vectored vaccines, such because the Oxford/AstraZeneca vaccine and the Sputnik V vaccine from Russia’s Gamaleya Institute. That is the place you are taking a innocent virus, reminiscent of a virus that provides you a chilly, and also you alter it in order that it will possibly infect one cell, however can’t reproduce and go on to contaminate different cells.
You then get that virus to hold the gene for a protein of curiosity, such because the spike protein of SARS-CoV-2, with the DNA sequence for the spike protein mixed into the virus’s DNA. The virus is thus a car for bringing the genetic directions on tips on how to make the spike protein into the physique.
The spike proteins (orange) are among the virus’s most recognisable antigens, so are goal for the immune system.
Kateryna Kon/Shutterstock
Once you vaccinate somebody with this innocent virus, it infects cells. The cells then learn the gene the virus is carrying and begin producing the spike protein, and the immune system mounts a response towards this. And since the physique recognises that there’s a virus current, the response it mounts could be very robust to the protein of curiosity and in addition to the viral vector.
The ultimate vaccines authorised are the brand new children on the block, the nucleic acid vaccines from Pfizer/BioNTech and Moderna. These are only a sequence of RNA wrapped up in a lipid droplet to cease it being degraded within the physique and assist it get inside a cell. RNA is a extremely delicate little molecule and is chopped up very simply and shortly if not protected. As soon as the RNA will get right into a cell, once more, it instructs the cell to make the SARS-CoV-2 spike protein for the immune system to reply to.
So how do you make these vaccines?
It depends upon the platform. For viral-vectored vaccines, you are taking a few of your innocent chilly virus after you’ve gotten added the spike protein DNA to it and develop it in a cell tradition. Though the virus has been altered so it will possibly’t reproduce within the physique, it will possibly nonetheless replicate within the specifically designed cells on this cell tradition.
You’ll then have this bulking up of the virus over the course of some days, anyplace from 4 litres of cell tradition as much as perhaps 20, 30 litres. Actually high-scale manufacturing will be carried out in metal tanks – the manufacturing atmosphere can look a bit much like a super-clean, sterile brewery. It’s important to ensure that your cells are in the most effective atmosphere doable for them to reside and to permit the virus to develop. This requires monitoring many environmental elements in and across the cell tradition – temperature, oxygen and CO₂ ranges, acidity and so forth.
You find yourself with this liquid that is filled with the virus that you simply’re inquisitive about. Nevertheless it’s additionally stuffed with supplies that you simply don’t need. So then you’ve gotten what we name downstream processing, the place you’re purifying the virus vaccine away from the entire different elements that you simply’re not inquisitive about.
That downstream course of is essential and is very managed and evaluated. It entails a number of filtration and chromatography. On the finish you need to have a really secure sterile product that comprises solely what you need.
There are a number of steps, and at every stage you’re taking samples and working experiments to indicate that you simply’re purifying your product as you go alongside. Regardless that it will possibly take just a few days to develop a batch of virus, it will possibly take a very long time to purify it and show that it’s pure, sterile and is what you say it’s. The vaccine will solely be launched when you may show that it’s the precise purity, sterility and composition that you simply’re claiming.
For inactivated vaccines, the method is comparable. You develop up litres of the virus itself. And then you definately kill it in a selected means so that you simply keep the construction of that lifeless virus. And then you definately take that and also you inject it into individuals.
The important thing ingredient of the Pfizer/BioNTech and Moderna vaccines – mRNA – is constructed piece by piece utilizing a synthesiser.
BioNTech/EPA-EFE
However making an mRNA vaccine is totally different?
Sure, with the nucleic acid vaccines you don’t have any cells. You don’t want any vats to develop something in. You utilize a machine, a synthesiser, so as to add every nucleic acid onto the following in the fitting sequence in order that you find yourself with the full-length RNA sequence that encodes the spike protein.
Then you need to take that and blend it along with your little lipid droplets. You combine these elements collectively in a really managed means so that you simply’ve produced these tiny little droplets which can be on the nanometre scale, along with your RNA on the within, lined by these lipids.
And once more, you need to analyse them and present that they meet a really tight specification of dimension and what they’re composed of and have the ability to show the standard of your product.
