Here’s a reminder that mRNA isn’t magic – and a reminder that we all were very, very fortunate that the technology worked as well as it has during the pandemic. Moderna released results for their flu vaccine program, because they (and others) are trying to work up a combination coronavirus/influenza vaccine. And the data are. . .OK. Not particularly better than the other influenza vaccines that are available, and perhaps actually a bit inferior. I see that there are headlines about how it worked well, that it produced “robust antibodies” against all four flu strains, and so on, but take a look at Moderna’s stock if you want to see a more useful reaction (it’s down in premarket). This is a better headline, and it makes an interesting contrast with the actual URL, doesn’t it? Influenza is a different problem then the coronavirus, for sure. There are four different species, each in its own genus (influenza A, B, C, and D) that all infect humans. Influenza B and C are mostly human diseases, and influenza D has mostly been seen in other species, although it can and does cross over into people. Influenza A is the one that we encounter most, though. It has a big reservoir in various bird species, and is also found in farm animals like pigs and horses. It can cross between species pretty readily, and to make things more fun, it comes in all sorts of subtypes. These are generally classified by the variations in two key proteins, haemagglutinin (H, with 18 main forms) and neuraminidase (N, with 9 main forms). That’s why you hear about things like “H1N1” and “H3N2” and the like – those are all types of influenza A, and of course there are variations among those as well. When you get really specific, you’ll see that H-N code, a year, a species (goose, whatever), and more. Like the finest French champagne, it’s vintage-dated. (I couldn’t resist. Here’s what that refers to, if you’ve never seen it – muwahaaa!) And the flu viruses have another notorious weapon. All pathogens are subject to antigenic drift, the gradual accumulation of mutations under various sorts of selection pressure. We’re seeing that with the current coronavirus, of course. But the flu virus genome is arranged in a more segmented fashion, allowing for mixing-and-matching of various strains inside a particular species, a process known as antigenic shift. For example, if different strains of influenza A infect the same cell – not a remote possibility, unfortunately – they can exchange genetic material and produce new forms of the virus bearing various pieces of each starting strain. We should be very glad that the coronaviruses don’t do this, because (as you can well imagine) that complicates things enormously for host organisms like us. And that’s why there’s a new flu vaccine every year, because this sort of thing is going on constantly, and it’s also why it can be quite hard to predict which strains are going to be the main source of trouble each season. Some of the less-impressive points about the Moderna data are that seroconversion didn’t seem to be as robust across different flu types(especially the influenza B ones), that the response was definitely lower in older patients (as compared, for example, to the exisiting Fluzone from Sanofi), and that all this was after two shots instead of one from competitors. Moderna emphasizes, as do the others working on mRNA influenza vaccines, that the shorter lead time of the technology could allow for better strain-matching as the virus changes from year to year, and is also talking up the possibilities for a wide ranging multi-respiratory-virus shot. Both of those could be true, but remain to be proven in practice. Pfizer and BioNTech are in this competition, as are GSK (partnered with CureVac), and Sanofi (via Translate Bio). We’re going to be seeing a lot of clinical data on these candidates, as well as more from a larger Moderna trial, so we’re in the early days. Don’t assume that mRNA is out of the flu-vaccine picture, then. But don’t assume that it’s a technology that will sweep everything else away, either – that’s the lesson from these data. Immunology is still immunology; we have no keys yet that will unlock all those doors. And it’s still true that the only way we have to sort all this out is in human clinical trials, so I’m actually glad to see several different organizations bringing different approaches to bear. If there is (or can be) an mRNA advantage in this area, I hope that increases the odds of finding it. But whether there is such a thing is, well, no sure thing.

This content was originally published here.

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