Issue #47: COVID-19 vaccines and influenza vaccines: Part 1

Written by Nobel Laureate Professor Peter Doherty

When we say COVID-19 we’re talking about the disease caused by infection with variants of the SARS-CoV-2 virus. The term ‘influenza’ (the flu), on the other hand, describes a respiratory syndrome caused by different influenza A and B viruses with, as mentioned last week (#46), as many as four different pathogens being targeted by our annual influenza vaccines. As SARS-CoV-2 variants emerge we are, of course, concerned that the current COVID-19 vaccines (#43, #44, #45) based on the original spike protein – from the virus isolated in Wuhan back in December 2019 – will indeed protect against novel strains first identified in the UK, South Africa, Brazil and so forth. Still, the rate of SARS-CoV-2 mutation is low when compared with the situation for the flu viruses.

In fact, with the various preventive measures – hand washing, masks, social distancing, lockdowns – we’ve taken for COVID-19, the incidence of influenza and other respiratory virus infections has dropped dramatically over the past year. That has provided welcome, if temporary, relief as, even with annual vaccine reformulation, infectious diseases specialists are increasingly concerned about our capacity to keep pace with the rapid, global dissemination of mutant influenza virus strains. Contributory factors are likely to be the steady growth in the size of the human family, along with the ramp-up in passenger air travel that has, for a time, been massively slowed by COVID-19.

The current COVID-19 vaccines are thus directed at one protein (the spike) from one virus, while the most commonly administered influenza vaccines are priming us to respond to three or four different influenza hemagglutinin (H) proteins from two flu A and one or two flu B viruses (#46). The flu example certainly tells us that there is no problem with overloading the immune system by asking it to respond simultaneously to four different proteins delivered in the same vaccine dose, a reality that is familiar to immunologists but not necessarily to the broader community. We should be reassured that making and delivering a vaccine specific for several variants of the SARS-CoV-2 spike could be a relatively straightforward process.

Though some influenza vaccines are now being made by the kind of recombinant protein technology that will be used if the COVID-19 Novovax vaccine (we are signed-up for it) is manufactured here – should that happen I’ll discuss it in a later essay – most flu vaccines are still made by a very traditional process. Large amounts of the different viruses are grown-up separately in embryonated hen’s eggs, inactivated by chemical treatment (likely using b propiolactone) to ensure that they are no longer infectious, then ‘split’ to purify the influenza H ‘subunits’. Years back, I visited such a plant in Swiftwater (#4), Pennsylvania, and was impressed with the ‘machine-industry era’ process. As I recall, a device sliced off the tops of the infected (by injection) eggs, then a robot arm tipped the virus-rich allantoic fluid that surrounds the chick embryo into a large container. Everything else was discarded. This type of approach is both expensive and ensures a very limited vaccine supply. The different viruses are grown up sequentially and, as flu vaccines are the only product made in this way, there are few facilities across the planet. Manufacturers are looking closely at the spectacular results with the new mRNA COVID-19 vaccines (#44).

Now in widespread use in South East Asia and Brazil, the Chinese Sinovac vaccine is comprised of chemically-inactivated SARS-CoV-2 virus that has been grown up in cell culture, with an added (and also very traditional) aluminium hydroxide ‘adjuvant’. Western vaccine developers avoided this type of approach for a number of reasons, including concerns about possible side effects. Early experiments in monkeys immunised with comparable ‘killed’ vaccine candidates for the original, 2002-3 SARS virus raised the spectre of possible immunopathology mediated via ‘enhancing antibodies’. Based on our understanding of the disease haemorrhagic dengue, the idea is that some vaccine-induced Ig molecules (#21) bind to the challenge virus and, instead of blocking infectivity, ‘help’ it to invade cells (particularly macrophages) that would not normally be at risk. That type of thinking is one reason why some feared that producing a safe SARS-CoV-2 vaccine might be very difficult. However, while a close watch has been kept for such effects in the various clinical trials, all the COVID-19 products, including the Sinovac formulation, look to be safe.

Another strategy is to use a live-attenuated vaccine, a strategy that has long been used in Russia. At least in Europe and the USA (it’s not available in Australia), the quadrivalent, live-attenuated Medimmune flu vaccine is given as a nasal spray, half into each nostril. Many would prefer that to being ‘jabbed’ with a needle. Medimmune was also, for a time at least, the vaccine of choice for many northern hemisphere paediatricians, who had serious concerns about the safety of one of the killed flu vaccines (not used here) deployed to counter the 2009 pandemic H1N1 virus.

Many of our best vaccines (e.g. measles, yellow fever) are ‘live-attenuated’ variants made decades back by serial passage in animals or tissue culture. What this actually involved was the selection of avirulent mutants with very limited growth potential in humans. Next week we’ll go on with this comparison of COVID-19 and influenza vaccines, beginning with further consideration of the live-attenuated approach.