Wherefore art thou, Novavax? Well, finally before an FDA advisory committee meeting for their coronavirus vaccine, that’s where they art. Here are the briefing documents, and here is the FDA’s analysis slide deck. It has been a long time, pandemically speaking, much longer than they or anyone else wanted. They have had sourcing/supply chain delays, manufacturing delays, clinical trial delays, still spät kommt er, doch er kommt. 

A brief reminder of what this vaccine is, and how it differs from the others approved for use in the US. An easy way to summarize it would be to say that Novavax’s candidate is by far the most traditional vaccine that we’ve seen in this country so far. The Pfizer/BioNTech and Moderna vaccines are of course mRNA-based, and that’s a mode of action that had not been used in humans before. The J&J vaccine is an adenovirus vector, and that as well had never quite made it to prime time in human vaccination, either (the AstraZeneca vaccine, which was never offered in the US, is another adenovirus one). All of these have something in common: one way or another, they relay on the vaccinated patient’s cells to make the viral antigen Spike protein that set off the immune response. But the Novavax vaccine is a direct injection of that Spike protein itself, along with an adjuvant (a separate ingredient that excites the immune system further).

We already have vaccines like that on the market – GSK’s shingles vaccine (Shingrix) is a recent example, and so is the papillomavirus (cervical cancer) vaccine Cervarix as well as the Merck one, Gardasil. The many various DTaP vaccines (diphtheria, tetanus, and pertussis) are all proteins plus adjuvant as well. In many of these, the adjuvant is an aluminum compound, often just good old aluminum hydroxide, which has been used for this purpose since the 1930s, but there are others. The adjuvant in Shingrix is basically the same as in the Novavax vaccine, a blend of compounds from the Chilean soap tree and some bacterial surface antigens. Back when the blog was sort of all-vaccines all-the-time, various vaccines and adjuvant combinations came up constantly.

It’s believed that there are a good number of people who would prefer to take something like the Novavax vaccine over the less-established techniques like mRNA and adenoviruses. I should add that over the last couple of years I have heard a number of comments, both in person and online, from people saying at the time that they would rather take the J&J vaccine over the mRNA ones, because they were under the impression that it, too, was a more traditional one – but as mentioned, that’s not the case. Novavax really is the first “classic” option to be offered in the US.

So how well does it work, and how safe is it? That’s what the advisory committee is hashing out today, and if you want live updates, I would suggest following Helen Branswell on Twitter. There has already been controversy about indicidents of myocarditis during the trials, which is quite interesting, because that’s been an issue to some degree with several other vaccines as well. It seems that it’s not something to do with the mRNA or the adenovirus platforms per se, since we’re seeing it here (edited because there has been far less sign of it in the adenovirus vaccines). What’s in common is the Spike protein. Novavax, it must be said, disputes that there is a relationship with its vaccine, saying that there is not enough data, but the signals seem stronger than were seen with the other vaccines, so we’ll see how that argument flies. Expect that to be a big topic of discussion as the day goes on! The age dependence will be much scrutinized – other vaccines have shown that younger patients (teenagers) seem at most risk, and several of the Novavax cases were in young men. But for this vaccine and the others, the myocarditis has been much milder than “regular” viral myocarditis infections, which is good.

Past that, though, this is going to be a difficult decision. Novavax’s clinical data are (almost entirely) from before the Delta and Omicron eras of coronavirus, which makes you wonder how it’s holding up under the current conditions (a constant problem with this constantly evolving virus). And the company’s extended manufacturing problems seem to have led to another complication: as Branswell noted earlier today, the FDA has now stated that the manufacturing situation “does not allow for a determination of comparability between the vaccine product used in these three studies and the vaccine product intended for use under EUA“, which is quite something. There are persistent questions about how this vaccine will fit into the current landscape (for example, does it qualify for “emergency use” when there are other vaccines available?) But even the FDA seems to be buying the idea that having the Novavax option might persuade some reluctant groups to finally get some sort of vaccination, so I don’t think that’s going to be a sticking point.

Overall, I would expect the advisory committee to recommend approval, but with a lot of post-EUA surveillance and data collection, and I would expect the FDA itself to follow suit. But this vaccine is never going to be a huge part of the battle against coronavirus, from the looks of it. If this had been the first one to hit back in 2020, the world would have jumped for it, but those days are gone. Novavax finds itself two years later fighting a changed virus in a changed world.