Issue #49: COVID-19 vaccines and influenza vaccines: Part 3, the 90% surprise

Written by Nobel Laureate Professor Peter Doherty

As discussed earlier in this series, our initial thinking on confronting the novel, rapidly spreading respiratory infection we’ve all come to know as COVID-19, was very much conditioned by the long human experience with that historic scourge, influenza, the dreaded flu. Both diseases can be characterised by severe pneumonias that, in the beginning at least, seemed to be broadly similar. When the key US regulatory agency – the Food and Drug Administration (FDA) – put out the guidelines for what might be regarded as an approvable vaccine for blocking SARS-CoV-2 infection, they set the bar low at 50 per cent efficacy. That is, after all, what the informed community generally accepts for influenza.

Reflecting on that 50 per cent number, you may recall from the two previous essays (#47, #48) that, when we talk about a COVID-19 vaccine, we are requiring protection against one virus while, with flu, we’re summarising the situation for three or four different viruses that share similar disease profiles. In fact, flu vaccines may be 70 per cent effective for, say, the currently circulating H1N1 variant, while as low as 30 per cent for the comparable H3N2 strain. Contributing to that diversity in efficacy, the fact that all flu viruses mutate at a very high rate (much faster than SARS-CoV-2) means that any one of the flu strains chosen six months or more back for inclusion in the vaccine cocktail may have changed to the extent that the mismatch can be too great for immunisation to provide any real protection. We can, as a consequence, have a ‘bad flu year’ that’s down to just one of the influenza A or B strains (#46).

You might find it interesting to understand a little of what happens here. The six World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza (Atlanta, Beijing, London, Memphis, Melbourne, Tokyo) have the job of monitoring what’s happening with influenza viruses across the planet. Most are primarily focused on what’s happening in people but one (Memphis) concentrates on the evolution of flu strains in other vertebrate species, especially water birds, domestic chickens and pigs. These WHO flu centres are supported by the national governments of the countries where they are located, with the Melbourne branch led by Kanta Subbarao and Ian Barr being part of our Institute. They collect virus isolates from Nation States in their region, often from National Reference Laboratories (both in the human and animal industry sectors), sequence them to see what variants are circulating and share information and reagents across the network. Representatives from all six centres then meet twice a year at WHO headquarters in Geneva to select the virus variants that the WHO will recommend for the separate northern and summer hemisphere vaccines.

That information is passed on to the manufacturers who, if they are using the old chick-embryo virus production method, will make three or four sequential batches of virus to be cleaned up, inactivated and incorporated in the vaccine. The WHO flu researchers also keep a weather eye on what’s happening with other respiratory virus infections and have been heavily involved in the global response to the coronaviruses, both SARS-CoV-1 and SARS-CoV-2. Given the magnitude of the SARS-CoV-2 problem it is likely that, if this virus continues to circulate and change in future years, monitoring may piggy-back (or be modelled) on the WHO flu mechanism, which has long been one of the most effective WHO operations. There will definitely need to be a close, globally coordinated watching brief for novel CoVs that have jumped into species that form part of the human food chain and may further cross into us.

When the first results came in from the Pfizer BioNTech vaccine phase 3 trials, the reports of 90 per cent efficacy in preventing severe disease had everyone over the moon. Many of us had long been of a mind that it should be reasonably straightforward to make a vaccine, but I doubt that anybody expected that level of success. The results we were hearing at first for the AstraZeneca phase 3 trials were less clear with, depending on some variations in the dosing regime and location of the trials, the demonstrated efficacy levels ranging from 60 per cent to 90%. By this time, of course, the public mind had moved way beyond the 50 per cent flu vaccine criterion, so AstraZeneca was starting out as a dog with a not so good name. Subsequently, as these two vaccines have been deployed across the UK, beginning with frontline healthcare workers and those in the most vulnerable groups, protection (against severe disease) in the 80-90 per cent range is being seen with both vaccines for all age groups though, I think, those at greatest risk were generally given the Pfizer product early on. Still, what’s even more encouraging, is that these results have been recorded for populations where the great majority have yet to receive their second, booster shot, as mandated for both vaccines.

So, what’s happening here? Why are these SARS-CoV-2 vaccines so much better than the flu vaccines? Is it that the technologies are different and all we need do to optimise flu vaccines will be to move to an mRNA strategy (#43)? Or could it be related to the nature of these infections and how and where these vaccines do their job? That’s where we’ll go next week.