COVID Transmissions for 6-16-2021

Novavax vaccine results: another great vaccine

Jun 16, 2021

Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.

It has been 576 days since the first documented human case of COVID-19. In 576, St. Germain of Paris died. St. Germain happens to be one of my favorite liqueurs, but I’m not sure if there’s a connection since it was first created in 2007. Still, I recommend mixing St. Germain about 1:3 or 1:4 with cold champagne or Prosecco for a nice refreshing cocktail. No, I don’t have a sponsorship deal with them. It’s just that summer is coming on, and I’m happy to share things that might help you enjoy it.

Speaking of things that might help us all get back to normal life, we have some new vaccine data to walk through today, and then some reader discussion about myocarditis.

Bolded terms are linked to the running newsletter glossary.

Keep COVID Transmissions growing by sharing it! Share the newsletter, not the virus. I love talking about science and explaining important concepts in human health, but I rely on all of you to grow the audience for this, which you can do by using this button here:

Share COVID Transmissions

Now, let’s talk COVID.

Novavax vaccine results

We were recently greeted with results for the Novavax vaccine, which demonstrated 90.4% efficacy against COVID-19 and 100% efficacy against severe disease and death. Novavax was a struggling company before the pandemic, and this vaccine success has likely saved it, at least on some level.

The vaccine they have made is a subunit design, meaning it mimics a subunit of the pathogen that it targets. Unlike other vaccine options, it does not use nucleic acids to express parts of the virus after vaccination. Instead, it contains all of the antigen that it delivers in the initial dose. For those who have—irrationally—raised concerns about nucleic acids in other vaccines, I doubt this will have much of an impact on hesitancy. However, I do expect that it will have an impact on vaccination logistically speaking. The vaccine is stored, and stable, at typical refrigerator temperatures. The more options that we have that can survive in those kinds of conditions, the better.

Another important element of these vaccine results is that while the trial was being conducted, variants such as B.1.1.7 were widely prevalent. This allowed the study to perform analyses of efficacy against specific variants of concern. With regard to the secondary endpoint of efficacy against such variants, the vaccine showed 93.2% efficacy, within the same general range as its efficacy against COVID-19 overall.

It’s great that this was included as part of the design of the trial, because it would have been the first question I would have asked otherwise. With these variants gradually replacing the original lineage, it’s important to demonstrate that any new vaccine will work against them as well.

Something that I think needs more focus is the reported preliminary safety profile of this vaccine. It seems that serious adverse events are quite rare, and the vaccine is overall mild on patients. This is really good news too—but the safety information provided are pretty scant, so I don’t want to comment too far before we have details.

I’ve heard some negative reactions to this vaccine in the biotech press, and I can’t figure out why. I think it’s great news to have another vaccine. Sure, the US market is essentially sewn up, but there are still billions of people around the world left to vaccinate. The more the merrier, particularly when the efficacy is so high. Now it just needs to go through the approval process.

Here’s the press release about the vaccine: https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-90-overall-efficacy-and

And here is some additional coverage in Science magazine: https://www.sciencemag.org/news/2021/06/powerful-new-covid-19-vaccine-shows-90-efficacy-could-boost-worlds-supply

What am I doing to cope with the pandemic? This:

Running into virologists in the park

Yesterday, finishing up my usual Tuesday run, I saw an old friend who happens to be a prominent COVID-19 virologist, in the park. We spent some time catching up, having a conversation without masks at a relatively normal distance. I think this is really what drives home for me that we’ve reached a safe point here in the US, at least if you’re fully vaccinated.

This may not last forever (or maybe it will!), but it was a moment of real normalcy for once, and it was great.

Reader Sam had some thoughts about the potential myocarditis issue with the Pfizer vaccine in adolescents/young males:

Re: myocarditis -- what about the mRNA vaccines might be causing the problem? In a recent article in Pediatrics examining the issue (https://pediatrics.aappublications.org/content/early/2021/06/04/peds.2021-052478) it was proposed that it might be related to the increased systemic reactogenicity seen (along with increased immunogenicity) in younger patients. If this is the case, might it be addressed by decreasing the dose, or changing the timing of the second dose? Are there any other plausible explanations? (This is the only one I've seen suggested.)
I'm a little concerned about what this means for vaccinating children under 12. Myocarditis tends to peak in younger men, but also in very young children (peaking in infancy, declining steadily over the following couple of years or so until reaching the baseline). And for the latter, it is more frequently severe. Pfizer has settled on a 3-µg dose for children aged 2-5 -- one-tenth that given to all ages so far -- which I hope mitigates this concern. But how could we know without a much larger trial?

These are some pretty deep questions regarding this, so while I provide my thoughts, let’s keep in mind that we know very little at this time—including whether or not the vaccines are the actual direct cause of the observed myocarditis. Here’s my reply:

“Increased systemic reactogenicity” is a fancy way to say these vaccines cause inflammatory reactions in the whole body. Myocarditis is, itself, an inflammatory reaction. So, I’m not into that as an explanation because it seems kind of circular to me—myocarditis, an inflammatory reaction, happens because the vaccine causes systemic inflammatory reactions? We can do better than that.
It seems to me that this systemic reactogenicity—as well as immunogenicity—are due to the ability of these vaccines to attract immune responses. In my opinion, that is because introducing non-self nucleic acids can activate several different immune pathways that attract and induce wider systemic responses. I think what’s happening is that these vaccines induce cytokines, those cytokines cause systemic effects, and in some people, that leads to myocarditis. This isn’t a much more satisfying explanation, I realize, but I think it’s a better hypothesis-generating explanation. We should investigate the cytokine response to mRNA vaccination, and understand the profile of the immune response they generate. I hypothesize that there is a specific cytokine or pattern of cytokines that, in very rare circumstances and in very specific patients, can encourage myocarditis.
If that’s true, then it’s possible you’re right—spacing out the vaccines a little further might help avoid the effect. Except, I’m not sure the effect is serious enough to bother with this. Myocarditis goes away and doesn’t seem to have been serious in anyone affected. It might be best just to manage it medically if it is detected.
As far as changing the dose in adults and older children, this isn’t going to happen. The dosing trials were conducted a long while ago, and the dose that went into Phase 3 is essentially locked in without another Phase 3 trial. Since the dose was carefully calibrated to be immunogenicity, I don’t think that there is much upside to trying to mess around with the dose here. Since the myocarditis effect—which is still unconfirmed—is very rare, it would be hard to detect any effect of a dosing change in the few patients per million who are actually impacted. It would also be more likely to compromise the efficacy that is observed with the current dosing. Since even if real, the myocarditis situation doesn’t seem to compromise the vaccine’s risk-benefit profile, I don’t think it is a worthwhile investment of resources to perform such a trial.
For younger children, I think it’s a valid question, but I’m still not very deeply concerned about the impact of this. This is a manageable and extremely rare condition, and it’s not at all clear that it’s vaccine-emergent. The reduced dose may have a positive impact in this younger population, but since we don’t know what’s actually causing this pattern to emerge I’m hesitant to speculate about what might happen. Because the signal is so rare, it may come down to postapproval monitoring to figure out if this is happening in younger patients. Considering the potential debilitating threats posed by COVID-19 in all ages, the FDA advisory committee reviewing the expanded authorization will need to carefully consider the potential risk-benefit. By then I suspect we will also know more about the patient circumstances in the observed cases, and perhaps understand the causality here better. Let’s return to this line of questioning when we have more information.

You might have some questions or comments! Send them in. As several folks have figured out, you can also email me if you have a comment that you don’t want to share with the whole group.

Join the conversation, and what you say will impact what I talk about in the next issue.

Also, let me know any other thoughts you might have about the newsletter. I’d like to make sure you’re getting what you want out of this.

Viral Transmissions

Discussion about this post