Issue #83: Viruses, Vaccines and COVID-19: possibilities on the vaccine front

Written by Nobel Laureate Professor Peter Doherty.

Last week we summarised what the SARS-CoV-2 virus is, and how it gets into our cells by attaching via the RBD (receptor binding domain) on its surface ‘spike’ (S) protein to the ACE2 molecules expressed on the outer (plasma) membrane of cells throughout our body. Now we’ll review the various vaccines, both existing and notional, that are designed to stimulate the production of antibodies (or immunoglobulins, Igs) that will block that RBD/ACE2 docking event while also ‘labelling’ the SARS-CoV-2 particles (virions) for possible destruction by other ‘innate’ defence mechanisms, like phagocytosis and complement binding (#19, #20). For now, we’ll ignore any ‘adverse events’ related to the vaccines as it’s my intent to discuss these later as a direct comparison with what happens for infection (the disease we call COVID-19) versus vaccination.

When it comes to the vaccine-hesitant, vaccine-hostile and/or needle-phobic, there is a SARS-CoV-2 vaccine strategy that many should find acceptable. We’re talking about single-dose, ‘live attenuated’ (or weakened) vaccines that could, for COVID-19, simply be ‘blown up the nose’ to give a very mild infection (#48). Such vaccines have long been made by taking a viral pathogen, then serially passaging it through successive cycles of replication in a different species (mice, yellow fever vaccine) or in cell cultures (measles, mumps, rubella, Sabin polio). Along the way, the virus mutates as it ‘adapts’ to grow better in its new ‘host’ and less well in us.

The most familiar is the Sabin polio vaccine. Given as a drop of liquid containing virus on a sugar cube, the Sabin virus infects cells in our gastrointestinal tract and, mimicking the natural infection, is very effective at generating a strong immune response. But the negative is that Sabin can ‘back-mutate’ (revert to virulence), which is why such live virus vaccines must be tested very thoroughly. When people worry about the ‘speed’ with which the SARS-CoV-2 vaccines have been developed, this is what their concern may be largely about. Also, for those who think that vaccinated people can infect others with the vaccine strain they’ve been given, that can only happen with these live-attenuated products.

With the blown-up-the-nose varieties, Russia has used ‘weakened’ influenza vaccines successfully for decades. FluMist, which has been given widely to children and adults under 60 in the northern hemisphere, contains live influenza viruses that have been adapted to grow at the lower temperature (25oC) of the nose (#12). Now, using modern molecular technology, live-attenuated vaccines that should be very safe are being made by directly manipulating the viral genome (#6). One such, COVI-VAC, has passed successfully through pre-clinical trials in animals (#57) and, if the worst-case-scenario of SARS-CoV-2 immune-escape variants happens (#64), could still play a part in this pandemic.

When it comes to needle avoidance, a strategy with great potential – especially for children – is the ‘microneedle patch’. Multiple, tiny spikes are embedded in a patch that just sticks to the skin and causes no more irritation than one of those small, circular wound plasters. The spikes, which are no wider than a human hair, only penetrate the very outer layer of the skin (the epidermis) and they can, for instance, be made of biodegradable sugars that are absorbed into the body. With the vaccine coating applied back at the time of manufacture or ‘in the field’, these could be used to deliver many different types of products. Apart from the ‘non-invasive’ means of delivery, there’s an immense saving on needles, syringes and so forth. Hopefully, we’ll see this strategy rolled out widely over the next decade, but they aren’t there yet.

The SARS-CoV-2 vaccines that are in general use but are not licensed in Australia are various types of ‘killed’, or inactivated products. Prominent among these are the Chinese Sinovac and Sinopharm vaccines that have been widely deployed in China, Indonesia, South America and many other countries (#47). The influenza vaccines we receive regularly are all of that type. The viruses are grown up in cell cultures or in embryonated hen’s eggs (an approach used only with flu), then the viral proteins are ‘purified’ to a greater or lesser extent and ‘inactivated’ by treatment with chemicals like formalin or beta propiolactone. Inactivated vaccines are generally injected with some form of ‘adjuvant’ (alum is commonly used) to stimulate the ‘innate’ immune response that helps ‘set-up’ the lymph nodes to develop an effective, virus-specific, adaptive immune response (#39, #42).

The ‘killed’ SARS-CoV-2 vaccines contain a much wider spectrum of viral proteins than the ‘spike-only’ vaccines used in Australia. Sinovac, for example, gives a good level of protection, though it also seems that there’s considerable benefit from a third shot, either with the original product or with one of the mRNA vaccines. The Chinese vaccines have been recognised by the TGA for allowing people to travel to Australia.