08 Feb 2021
Issue #43: Virus and vaccine - Part 1
Written by Nobel Laureate Professor Peter Doherty
What the SARS-CoV-2 shares with any other viral pathogen is that it’s bad news (for us) wrapped in a bit of protein and fat (lipid), with some sugars stuck here and there on the outside. We’ll forget the sugars for the rest of this, and the protein/lipid capsule/envelope is just there to protect the bad news – the 30,000 base pair RNA genome (#6) – as the virus particle (virion) makes its way passively from cell-to-cell, from person to person. One of the proteins it doesn’t have is myosin (the building blocks of muscle), and it has no ‘motor’ to move itself around. And, apart from those in the capsule that protect the RNA, the protein that concerns us most is the spike protein that sticks out from the surface of the virion and, via the receptor binding domain (RBD), sticks tightly to the ACE2 molecule on the surface of our cells (#17, #18). That high affinity receptor/ligand interaction (#22) triggers the entry of the whole virus particle into the cell, where it breaks apart to free its RNA information system and begin the process of reproducing itself.
The Australian Government has signed us up to date for three different vaccines, and we expect two of them to begin rolling out within a month or so. All look good when compared with, say, the standard influenza vaccines, and I’ll take whatever I’m offered as soon as I’m offered it. All of them are focused on the spike protein and none of them can revert to be infectious virus. The BioNTech/Pfizer vaccine is made up of the viral mRNA that is all that has to be added to the machinery and ‘food resource’ within our cells to make new SARS-CoV-2 spike protein. The manufacturers have encased that in a shell of lipid for protection – fat droplets are ‘eaten’ by cells – and, though the vaccine, can survive for a time in a standard refrigerator. The aim is to use it as quickly as possible after the vial is taken out of a dry-ice (-70C, solid CO2) or liquid nitrogen (-80C, N2) – the principal gas in the air we breathe – freezer. People will likely need to go to a hospital that has that level of resource if they are to be jabbed with this one.
The second vaccine – made here by CSL (#4) – is the AstraZeneca Chimpanzee Adenovirus (ChAd9) vectored vaccine that was originally developed at Oxford’s Jenner Institute. What the gene jockeys have done here is to paste the SARS-CoV-2 DNA (copied from the viral RNA) into the DNA of an adenovirus that can no longer reproduce itself due to having bits of its own DNA cut out (excised). The adenovirus coat is there to protect the nucleic acid sequence encoding the SARS-CoV-2 spike protein and, as the adenoviruses bind to a number of different receptors on the surface of cells, get it from outside to inside so that again, the DNA is released to begin making new spike.
The third product is the Novovax vaccine that went through its Phase 1 clinical trials here and can also be made in Australia by CSL. It looks to be a very good vaccine but, for technical reasons, it has been slow going into Phase 3 clinical trials and won’t be available for some months. This is comprised of spike protein that’s been made in big culture vessels and will be given with an adjuvant. The basic message is, though, that the SARS-CoV-2 product is ready made and doesn’t require any of our cell machinery for the manufacturing process. As we won’t be rolling it out soon, I’ll write more about it later. I should also point out that all these vaccines are made in ultra-clean, sophisticated, GMP (good manufacturing practice) facilities that are licensed by the key regulatory agencies, the US FDA (Food and Drug Administration) and Australia’s TGA (Therapeutic Goods Administration) that also approve drugs and vaccines for use.
In order to understand these vaccines (#4) better, we need to go back to the virus. Once the SARS-CoV-2 virus gets into the cell, it stays in the cytoplasm and does not (unlike many other viruses) need to enter the cell nucleus that contains most of the DNA – the information system for making us. Unlike the HIV retrovirus that causes AIDS, the CoVs have no reverse transcriptase that can copy viral gene sequences back into our genomes, which is one of the reasons that making a vaccine to protect against COVID-19 has been infinitely easier than making a vaccine to stop HIV/AIDS. The other reason is that HIV mutates at an extraordinarily high rate. Even so, the CoVs do mutate, and that is a concern re vaccination that I’ll write about soon, but we’ll leave it for the moment. Next week we’ll discuss the SARS-CoV-2 replication/reproduction strategy and tie that into the vaccines we’ve introduced above.