Re: mixing J&J and mRNA vaccines -- assuming this combination does produce a durable immune response, I wonder if it might decrease the incidence of myocarditis reactions? Perhaps interesting in this regard is an article published last week (https://www.mdpi.com/2076-393X/9/10/1186/htm) suggesting a mechanism by which the reaction occurs, and recommending increasing the time interval between doses as a way to mitigate it.
I'm not sure whether myocarditis is necessarily caused by cumulative exposure, so I don't feel totally comfortable speculating. I am interested, though, in the following paper that suggests that inadvertent intravenous (rather than intramuscular) injection of the mRNA vaccines could give rise to myocarditis: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab707/6353927
The intravenous vs intramuscular explanation (which is not necessarily mutually exclusive with what you shared, by the way) could explain why the event is so rare. It seems strange that cardiac inflammation would be caused, even transiently and in a very small subset of patients, by the injection of a small volume of mRNA into muscle. We know the mRNA is not very mobile and only persists for a couple of weeks, so if it is being properly injected into muscle, it shouldn't go anywhere, really, and the remote effect on the heart is at the very least surprising. In this explanation, accidental intravenous injection leads to dissemination of the mRNA more systemically, and when it reaches the heart it causes myocarditis. This doesn't sound too far-fetched to me, so I'd be interested to know if there is some way to further validate the hypothesis.
The paper I linked compares IV vs IM injection in mice. For the IV injections, they used the tail vein, so a good model for peripheral vein injection. But, these are mice we're talking about here. They're not all that close to human, so while I think the paper makes its argument well, I want some kind of confirmation in a clinical setting with humans.
What I'd like is if there is some clinical technique that could determine whether the injection site in patients with myocarditis post-vaccine resulted in a vein being punctured. I don't know enough about the techniques that might be deployed to do that kind of work.
Another option would be to try and deploy a proactive intervention to prevent venous delivery in a large population, and randomize patients to either that intervention or some sort of sham intervention. That seems like it would be way too much expense and effort, though, for such a rare adverse effect. Such a trial would need to be truly massive to even detect a difference between the intervention and non-intervention group.
Politico is claiming that Novavax still can't produce pure vaccine, and they predict that the FDA won't approve the Novavax product until next year at the earliest. I'm not totally persuaded (the story doesn't seem to know about their deal with the Serum Institute, for instance) but it's already crushing their stock price.
I had not seen that. I guess this is what you get when you bet $1.6 billion on a company that hasn't ever brought a product to market before. It's disappointing for sure--their vaccine appears to be work very well, when it is actually manufactured. Maybe they can make a deal with some more experienced concern that will help them get the job done.
I'm pretty sure there are few vaccine makers with more experience than Novavax's partner, the Serum Institute of India, the world's largest vaccine manufacturer.
Serum Institute is tooling up according to Novavax's specifications. I'm not sure how tightly partnered they are in terms of the actual process development, and if Novavax is giving them a process that doesn't meet FDA specifications, I don't know that this is going to change anything with regard to US use of the Novavax product. I don't think Serum Institute has produced anything to meet FDA standards either, so I don't know how much help they would be as a partner in this regard. Meeting those standards will only matter for US distribution, though. Other countries will have their own ideas about what is acceptable.
The AZ vaccine has had a whole saga of data preparation and process woes with FDA too. AZ has said a few times they’re still pursuing it, but at this point I think they’ve probably decided to focus on ex-US markets. I still don’t know whether that situation is primarily AZ or the FDA’s fault, but I suspect both parties got in the way of that vaccine being available.
It’s strange that two of the vaccines being most strongly considered for provision to Covax are also both having issues at the FDA, but probably just a coincidence.
Re: mixing J&J and mRNA vaccines -- assuming this combination does produce a durable immune response, I wonder if it might decrease the incidence of myocarditis reactions? Perhaps interesting in this regard is an article published last week (https://www.mdpi.com/2076-393X/9/10/1186/htm) suggesting a mechanism by which the reaction occurs, and recommending increasing the time interval between doses as a way to mitigate it.
I'm not sure whether myocarditis is necessarily caused by cumulative exposure, so I don't feel totally comfortable speculating. I am interested, though, in the following paper that suggests that inadvertent intravenous (rather than intramuscular) injection of the mRNA vaccines could give rise to myocarditis: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab707/6353927
The intravenous vs intramuscular explanation (which is not necessarily mutually exclusive with what you shared, by the way) could explain why the event is so rare. It seems strange that cardiac inflammation would be caused, even transiently and in a very small subset of patients, by the injection of a small volume of mRNA into muscle. We know the mRNA is not very mobile and only persists for a couple of weeks, so if it is being properly injected into muscle, it shouldn't go anywhere, really, and the remote effect on the heart is at the very least surprising. In this explanation, accidental intravenous injection leads to dissemination of the mRNA more systemically, and when it reaches the heart it causes myocarditis. This doesn't sound too far-fetched to me, so I'd be interested to know if there is some way to further validate the hypothesis.
Presumably you could test the IV hypothesis by injecting mRNA vaccine into an experimental animal's peripheral vein?
The paper I linked compares IV vs IM injection in mice. For the IV injections, they used the tail vein, so a good model for peripheral vein injection. But, these are mice we're talking about here. They're not all that close to human, so while I think the paper makes its argument well, I want some kind of confirmation in a clinical setting with humans.
What I'd like is if there is some clinical technique that could determine whether the injection site in patients with myocarditis post-vaccine resulted in a vein being punctured. I don't know enough about the techniques that might be deployed to do that kind of work.
Another option would be to try and deploy a proactive intervention to prevent venous delivery in a large population, and randomize patients to either that intervention or some sort of sham intervention. That seems like it would be way too much expense and effort, though, for such a rare adverse effect. Such a trial would need to be truly massive to even detect a difference between the intervention and non-intervention group.
Did you see this story?
https://www.politico.com/news/2021/10/19/novavax-vaccine-rush-process-global-campaign-516298
Politico is claiming that Novavax still can't produce pure vaccine, and they predict that the FDA won't approve the Novavax product until next year at the earliest. I'm not totally persuaded (the story doesn't seem to know about their deal with the Serum Institute, for instance) but it's already crushing their stock price.
I had not seen that. I guess this is what you get when you bet $1.6 billion on a company that hasn't ever brought a product to market before. It's disappointing for sure--their vaccine appears to be work very well, when it is actually manufactured. Maybe they can make a deal with some more experienced concern that will help them get the job done.
I'm pretty sure there are few vaccine makers with more experience than Novavax's partner, the Serum Institute of India, the world's largest vaccine manufacturer.
Serum Institute is tooling up according to Novavax's specifications. I'm not sure how tightly partnered they are in terms of the actual process development, and if Novavax is giving them a process that doesn't meet FDA specifications, I don't know that this is going to change anything with regard to US use of the Novavax product. I don't think Serum Institute has produced anything to meet FDA standards either, so I don't know how much help they would be as a partner in this regard. Meeting those standards will only matter for US distribution, though. Other countries will have their own ideas about what is acceptable.
Serum Institute is, I believe, the largest maker of the AstraZeneca vaccine. Not yet FDA approved, but no reason to think it would not be.
The AZ vaccine has had a whole saga of data preparation and process woes with FDA too. AZ has said a few times they’re still pursuing it, but at this point I think they’ve probably decided to focus on ex-US markets. I still don’t know whether that situation is primarily AZ or the FDA’s fault, but I suspect both parties got in the way of that vaccine being available.
It’s strange that two of the vaccines being most strongly considered for provision to Covax are also both having issues at the FDA, but probably just a coincidence.