I surveyed the coronavirus vaccine landscape in this post, and then detailed some of the larger efforts in the field here (several updates have been added to that one since its initial posting). Now it’s time to look at several programs that aren’t in either of those, but still have plenty of serious science behind them.
For an example of a relatively new technology that’s now in use for human patients, there’s the VSV (vesicular stomatitis virus) platform, which was used to produce the Ebola vaccine now manufactured by Merck. Stat has an excellent long-form article from earlier this year about how this came about, and it’s well worth a read, both for the history itself and as a look into the ups and downs of vaccine research in general. The Yale team behind that one had developed a promising vaccine candidate for the SARS coronavirus during its epidemic, and they’re using those lessons in their current work. If you look at that second link above on vaccine candidates, you will note that there are several using adenovirus vectors – this is conceptually the same sort of thing, but using a livestock virus (VSV) instead of human or primate-associated adenoviruses. I don’t know if the Yale team has partnered with anyone yet, but I should also mention another connection of theirs, a spinoff company called CaroGen that has another engineered virus platform that is also being put to use against SARS-CoV-2. These projects are aiming at FDA approval for Phase I trials, but there’s no word yet on what such an application might go in.
Novavax made headlines last week when the international Coalition for Epidemic Preparedness Innovations (CEPI) awarded them a $384 million dollar grant to develop their vaccine candidate, NVX-CoV2373. The company has had a pretty lively history in this area: a grant from the Gates Foundation allowed them to get their respiratory syncytial virus (RSV) vaccine candidate (ResVax) into human trials, but in late 2016 the Phase III failed to demonstrate efficacy. This happens distressingly often in the vaccine field, and we’re going to have to get ready for it to happen in human trials of coronavirus vaccines as well (which is why I’m glad that there are so many candidates in the works). But in March of this year they reported a successful Phase III with their seasonal flu vaccine, so they (and their technology, which includes their own proprietary adjuvant) are in better shape. Novavax is in the “recombinant viral protein vaccine” category; they use a common protein production method that involves insect cells (Sf9) that are genetically modified by baculovirus infection. That’s a pretty robust platform; it’s used in research organizations around the world and there are a number of commercial variations that have been engineered for efficiency and yield. People have been expecting this sort of thing to take over the viral-protein-fragment vaccine area for years now, and we’ll see if this crisis speeds things up. As for Novavax, their Phase I starts this month in Australia, and they’re hoping to move into Phase II trials after the results come out in July.
There are several ways to produce such vaccine protein antigens, and one that’s been looked at over the years is doing it in plants – specifically, tobacco plants. The tobacco mosaic virus (TMV) has been studied a great deal over the years as a model system, and this is what’s used to modify the plants to produce the desired protein. As with the insect cells, you have the advantage of doing this in a system that doesn’t have any human pathogens in it. The tobacco-produced proteins, moreover, can be pushed to quite high yields in the leaves, making purification an easier task, and growing the plants is easier than cell culture is. British American Tobacco (BAT) has a biotech arm in Kentucky that’s been studying this, and they have announced that their candidate vaccine has shown enough evidence to justify going into Phase I trials in humans. They’re hoping for late June for first dosing, and they’re not the only tobacco company looking at this idea. Some readers may recall that the tobacco protein production idea was used during the Ebola epidemic for production of a monoclonal antibody cocktail (ZMapp) – that one didn’t work out in the end, but it was not because of the production method.
As you can see, these efforts are behind the front-running candidates that I discussed earlier, but not by very much. I’m glad to see so many different techniques being brought to bear, because we’re going to need as many good shots as we can get, from all sorts of directions. The challenge will be where and how all these Phase II and III trials will be run, though – I have a feeling we’ll be chasing the epidemic to various parts of the globe to get the best data, and that’s a logistic problem, for sure. . .