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Another Set of Coronavirus Vaccine Candidates

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. . .

20 comments on “Another Set of Coronavirus Vaccine Candidates”

  1. Dr. Manhattan says:

    “respiratory syntactical virus (RSV)” above should read respiratory syncytial virus.

    1. Sol porter says:

      Well, its just a syntax error

  2. One important aspect that NOBODY discusses is the effect of residual non-target proteins in the vaccine. The Ebola vaccine, ERVEBO contains rice proteins, for example. What happens when you teach the immune system to attack rice proteins? Rice allergy. Details:

    ERVEBO Ebola vaccine will create a rice allergy epidemic, add to numerous autoimmune diseases, cancer and make Ebola disease even more severe. Design for safety and vaccine safety regulation remain abject failures. Incompetence or indifference?

    It is extremely important therefore for EVERY vaccine to be DESIGNED FOR SAFETY by using Failure Modes and Effects Analysis (FMEA). No vaccine should be approved unless FMEA is published.

    1. fef says:

      I think inducing tobacco allergy might actually have a positive effect on long term public health.
      (I am half-joking)

    2. Wallace Grommet says:

      Vinu is a notorious crank, prolix, CAPS ON, agitator, and vying for the title of most annoying person in human history (you have my vote) He leans on facts as a drunkard leans on a lamp post; for support rather than illumination

  3. JasonP says:


    Thank you AGAIN! For you continuing efforts to distill this information and educate!

  4. Fred the Fourth says:

    (From this technical but non-bio-savvy guy) Thank you.
    Your blog is a huge light in the mass of wrong or distorted information churning around the world.
    I can’t count the number of times I have come here for info to clarify some piece of poorly stated or outright wrong info my friends and family have heard from major media.
    Yet another happy victim of your first clickbait article, “Sand won’t save you now”

    1. loupgarous says:

      Derek’s sardonic and occasionally whacko wit is part of what brings me back, and part of it is Derek’s ability to summarize very complex concepts so even I can understand them. And part is the quality of the discussions here in the comment space – sure, we get trollers, but we also get the thoughts of remarkably smart folks..

      1. Fred the Fourth says:

        Yeah, but he has a glaring flaw.
        He’s afraid of nitrogen atoms. Or at least , big crowds of nitrogen atoms.
        How are we supposed to respect a guy like that?

        1. miles says:

          But he does feed starving komodo dragons

          1. loupgarous says:

            And Derek’s a strong advocate of neutering exotic pets. Say, hyenas.

        2. loupgarous says:

          He’s only bothered by many nitro groups in unreasonably close proximity that I can tell.

          HNIW/CL-20’s got two un-nitrated spots left in its “crown”. Go work with Prof. Dr. Thomas Klapötke, fill those spaces in, and (assuming you survive the process), you can ask how we can respect a guy who’s goosey about poly-poly-nitros.

          1. loupgarous says:

            Whoops. I take that back. Derek doesn have an azidoazide phobia (as ought we all) and has allocuted to a general polyazide aversion:

            ” I’ve made some of that sort, since azide displacement is a classic (and useful) way to get a nitrogen into your molecule. But the smaller ones aren’t worth the risk. That’s because the higher the percentage of nitrogens in the formula, the more you have to worry. Thermodynamically, nitrogens bonded to each other are always regarded as guilty until proven innocent – there’s always the fear that they’re going to find a way to throw off their civilized clothes and revert to wild nitrogen gas. That’s a hugely stable compound. If your structure goes that route, all that extra bonding energy it used to have ends up diverted into flying shrapnel and loud noises.

          2. Some idiot says:

            Er, I think the allergy also extends to far too many nitrogens with far too few carbons… Having said that, I (as a process chemist…) would consider it to be a very _healthy_ allergy…

            I remember all too vividly once when one of my colleagues (at a previous job) was starting up a new project, and was running through the known routes, and the ideas of what he would work on… I started thinking that it was a while since I had seen a “decent” number of carbons in the structures, and said “have any of these been safety tested yet?” and after a pause of a few seconds, a low chuckle ran around the room. After another pause my colleague said “Right. I’ll send everything to our safety guy before I do any lab work on them…!”

          3. loupgarous says:

            @Some idiot: You’re right, back in 2004 Derek’s made his feelings known about azidoazides (with little else in them).

  5. Nik says:

    Do you think companies will end up running human challenge trials eventually? Seems like the WHO is now on board with doing it too.

    1. loupgarous says:

      Do you think one of WHO’s friends in China suggested human challenge trials aren’t all that bad? Asking for a friend.

      1. myst_05 says:

        Dunno, I’m not Chinese but I’m willing to volunteer for such a trial.

  6. Michael D says:

    Derek, I want to echo the thanks so many readers post for your blog. I have learned so much.

    I ask this as someone who knows nothing about drug development and vaccine design. As studies are emerging that suggest that vaccines would benefit from targeting other proteins as well as the Spike, is it possible to tweak vaccine design currently in development, or must one start from scratch? For example, Johnson & Johnson is still several months away from human trials; do they have any opportunity to incorporate new information into their candidate, or are they already too far down the path of vaccine design?

    And if one does need to start from scratch, are there any players in the mRNA space that could try a new design targeting the additional proteins as well?

  7. I think the bit on ZMapp is not correct. It is my understanding that the tobacco-based production never really worked at scale and that they shifted production to cell culture, even for the trial quantities used in DRC. So, while I stand to be corrected, I’m pretty sure even if ZMapp had been effective, the plant-based production method was not.

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