Editor’s observe: Anne Moore is a senior lecturer in biochemistry and cell biology at College Faculty Cork and a specialist in vaccine improvement. We spoke to her for episode 3 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 completely different applied sciences, or “platforms”. Probably the most typical one is the inactivated vaccine. It incorporates lifeless virus. As a result of the virus remains to be entire, it has all the elements, within the appropriate form, that may stimulate a response from the immune system – what we name the antigens. The immune response may be towards a number of antigens.
The Chinese language vaccines – from Sinovac and Sinopharm – are the principle ones utilizing this platform. It’s an incredible know-how, it really works for some human and veterinary vaccines. The identical method 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’re taking a innocent virus, corresponding to a virus that offers you a chilly, and also you alter it in order that it might 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 automobile for bringing the genetic directions on find out how to make the spike protein into the physique.
Whenever 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 sturdy to the protein of curiosity and in addition to the viral vector.
The ultimate vaccines authorised are the brand new youngsters 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 very 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 will depend on the platform. For viral-vectored vaccines, you’re taking a few of your innocent chilly virus after you will have added the spike protein DNA to it and develop it in a cell tradition. Though the virus has been altered so it might’t reproduce within the physique, it might 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 possibly 20, 30 litres. Actually high-scale manufacturing may be carried out in metal tanks – the manufacturing atmosphere can look a bit just like a super-clean, sterile brewery. You must be sure that your cells are in the perfect atmosphere potential for them to dwell 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 stuffed with the virus that you simply’re keen on. However it’s additionally stuffed with supplies that you simply don’t need. So then you will have what we name downstream processing, the place you’re purifying the virus vaccine away from all the different elements that you simply’re not keen on.
That downstream course of is essential and is very managed and evaluated. It includes plenty of filtration and chromatography. On the finish it’s important to have a really protected sterile product that incorporates 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 might take just a few days to develop a batch of virus, it might 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 approach so that you simply preserve the construction of that lifeless virus. And then you definately take that and also you inject it into folks.
However making an mRNA vaccine is completely different?
Sure, with the nucleic acid vaccines you don’t have any cells. You don’t want any vats to develop something in. You employ a machine, a synthesiser, so as to add every nucleic acid onto the following in the proper sequence in order that you find yourself with the full-length RNA sequence that encodes the spike protein.
Then it’s important to take that and blend it along with your little lipid droplets. You combine these elements collectively in a really managed approach so that you simply’ve produced these tiny little droplets which can be on the nanometre scale, along with your RNA on the within, coated by these lipids.
And once more, it’s important to analyse them and present that they meet a really tight specification of dimension and what they’re composed of and be capable of show the standard of your product.
Anne Moore has, prior to now, acquired funding from grant-awarding authorities and thru collaborative analysis work with small and medium vaccine firms.