I’m not going to pretend that I know more about this beyond the surface-level (no pun intended) but it seems to me that if there’s only one mutation, then the I would expect a small commensurate change in vaccine effectiveness (which seems to be what we’ve seen so far).
There’s an idea called evidence-based medicine that’s popular in medicine lately. According to it one seeks to not extrapolate based on arguments like that but looks experimentally at what actually happens. What happens is:
Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant.
Moderna/Pfizer don’t make any promises that the vaccine protection is going to hold forever. An argument that they could have developed a better product is very far from showing that they have injured plaintiffs.
That said, developing better products isn’t free. It takes research. Updating the vaccine to Delta costs money. There’s no legal obligation to do that.
We’re both speculating based on different data. You’re citing an in vitro study using sera from individuals with one or two doses, and there’s some amount of mechanistic speculation in terms of how decreases in neutralization response and titers changes the ultimate outcome, which is case severity of vaccinated people exposed to Delta compared to unvaccinated people (at least in my mind). So far that still seems very positive.
Thinking in more of a comp sci way, it strikes me that there could also be a problem of over-fitting for a specific variant of the s2 subunit. Say Pfizer and Moderna thought about changing the mRNA to specifically match the Delta s2 subunit, but maybe they’re anticipating a world where the next more contagious strain doesn’t contain that s2 subunit mutation? Or maybe, like you suggested, it is just a cost-benefit thing.
Moderna/Pfizer don’t make any promises that the vaccine protection is going to hold forever. An argument that they could have developed a better product is very far from showing that they have injured plaintiffs.
Maybe. But it’s not that far. If they really had designs somewhere to make a vaccine that would last substantially longer and they scrapped them in favor of one that lasts 6-12 months… I just think the probability of the IP for the better designed being concentrated only in a few companies and not independently discoverable by other people is low, and the probability that it could be kept secret for months or years is low. The probability of the Frank Azars of the world hearing about that and taking a shot at litigating it for a piece of a very very large settlement seems high (low-risk, high-reward), but more likely I think Congress would amend or repeal PREPA under that circumstance and open the floodgates of lawsuits.
Say Pfizer and Moderna thought about changing the mRNA to specifically match the Delta s2 subunit, but maybe they’re anticipating a world where the next more contagious strain doesn’t contain that s2 subunit mutation?
When we do influenca vaccines we use multiple targets then just one to be able to vaccinate against multiple strains. Even if you assume that only 50% of future variants include the Delta spike protein you could give 50% alpha spike protein and 50% delta spike protein in your vaccine.
Ideally, I would expect a vaccine that’s designed to be resistant against mutations to go the RaDVaC way of targeting peptides in different proteins of the virus to prevent any single mutation from removing the protection.
Of course that means that you need to run studies to validate targets.
If they really had designs somewhere to make a vaccine that would last substantially longer and they scrapped them in favor of one that lasts 6-12 months.
Things are more complex then that. If we believe the Moderna people they essentially decided on the vaccine they wanted to produce within days after the Chinese finally decided to publish the full sequence including the full spike protein with it’s furin cleavage site.
Given that it was important to have a vaccine as fast as possible that was a reasonable approach. Creating a vaccine that’s more resistant to mutations takes work. The decision to stay with that vaccine instead of investing into creating a better version is an economic one for which you couldn’t persue a company in front of a court.
Given that it was important to have a vaccine as fast as possible that was a reasonable approach. Creating a vaccine that’s more resistant to mutations takes work.
The decision to stay with that vaccine instead of investing into creating a better version is an economic one for which you couldn’t persue a company in front of a court.
I’m not sure that Ralph Nader, for example, would entirely agree. Unsafe at Any Speed is analogous to the extent that car makers were optimizing for one set of conditions (cars that would get you laid) rather than another set (optimizing for cars that are less likely to kill you). What you’re saying here (correct me if I’m way off) is that vaccines were optimized for ease of manufacture and dissemination rather than providing more comprehensive long-term immunity, and that financial incentives are now against pharma companies optimizing for more comprehensive long-term immunity…
Our legal system (mostly legislative in this case) was still able to deal with this and car makers now are required meet safety standards.
But that being said I’m all for doing what can be done to make incentives less perverse. Maybe find someone biologically-savvy and bureaucratically-minded to draft an initial set of vaccine quality improvement guidelines. Like a Deming wheel but applied to increasing vaccine efficacy, and if you get federal money you have to follow. Those are hard problems to solve.
At the moment is sounds a little more like a toss up between a third shot and a delta-specific one.
In a reasonable world the change to a delta-specific one would have happened months ago.
What you’re saying here (correct me if I’m way off) is that vaccines were optimized for ease of manufacture and dissemination rather than providing more comprehensive long-term immunity
No, I think the choices were awful for the goal of ease of manufacturing. The goal was getting approval to bring the vaccines to market as fast as possible (the prelimary approval type).
In a pandemic, it’s good to have vaccines available sooner then later. That’s a different goal then optimizing for cars looking good.
There’s an idea called evidence-based medicine that’s popular in medicine lately. According to it one seeks to not extrapolate based on arguments like that but looks experimentally at what actually happens. What happens is:
Moderna/Pfizer don’t make any promises that the vaccine protection is going to hold forever. An argument that they could have developed a better product is very far from showing that they have injured plaintiffs.
That said, developing better products isn’t free. It takes research. Updating the vaccine to Delta costs money. There’s no legal obligation to do that.
We’re both speculating based on different data. You’re citing an in vitro study using sera from individuals with one or two doses, and there’s some amount of mechanistic speculation in terms of how decreases in neutralization response and titers changes the ultimate outcome, which is case severity of vaccinated people exposed to Delta compared to unvaccinated people (at least in my mind). So far that still seems very positive.
Thinking in more of a comp sci way, it strikes me that there could also be a problem of over-fitting for a specific variant of the s2 subunit. Say Pfizer and Moderna thought about changing the mRNA to specifically match the Delta s2 subunit, but maybe they’re anticipating a world where the next more contagious strain doesn’t contain that s2 subunit mutation? Or maybe, like you suggested, it is just a cost-benefit thing.
Maybe. But it’s not that far. If they really had designs somewhere to make a vaccine that would last substantially longer and they scrapped them in favor of one that lasts 6-12 months… I just think the probability of the IP for the better designed being concentrated only in a few companies and not independently discoverable by other people is low, and the probability that it could be kept secret for months or years is low. The probability of the Frank Azars of the world hearing about that and taking a shot at litigating it for a piece of a very very large settlement seems high (low-risk, high-reward), but more likely I think Congress would amend or repeal PREPA under that circumstance and open the floodgates of lawsuits.
When we do influenca vaccines we use multiple targets then just one to be able to vaccinate against multiple strains. Even if you assume that only 50% of future variants include the Delta spike protein you could give 50% alpha spike protein and 50% delta spike protein in your vaccine.
Ideally, I would expect a vaccine that’s designed to be resistant against mutations to go the RaDVaC way of targeting peptides in different proteins of the virus to prevent any single mutation from removing the protection.
Of course that means that you need to run studies to validate targets.
Things are more complex then that. If we believe the Moderna people they essentially decided on the vaccine they wanted to produce within days after the Chinese finally decided to publish the full sequence including the full spike protein with it’s furin cleavage site.
Given that it was important to have a vaccine as fast as possible that was a reasonable approach. Creating a vaccine that’s more resistant to mutations takes work. The decision to stay with that vaccine instead of investing into creating a better version is an economic one for which you couldn’t persue a company in front of a court.
Just doing some quick searching, it doesn’t sound like that’s the decision that they’re making. At the moment is sounds a little more like a toss up between a third shot and a delta-specific one.
I’m not sure that Ralph Nader, for example, would entirely agree. Unsafe at Any Speed is analogous to the extent that car makers were optimizing for one set of conditions (cars that would get you laid) rather than another set (optimizing for cars that are less likely to kill you). What you’re saying here (correct me if I’m way off) is that vaccines were optimized for ease of manufacture and dissemination rather than providing more comprehensive long-term immunity, and that financial incentives are now against pharma companies optimizing for more comprehensive long-term immunity…
Our legal system (mostly legislative in this case) was still able to deal with this and car makers now are required meet safety standards.
But that being said I’m all for doing what can be done to make incentives less perverse. Maybe find someone biologically-savvy and bureaucratically-minded to draft an initial set of vaccine quality improvement guidelines. Like a Deming wheel but applied to increasing vaccine efficacy, and if you get federal money you have to follow. Those are hard problems to solve.
In a reasonable world the change to a delta-specific one would have happened months ago.
No, I think the choices were awful for the goal of ease of manufacturing. The goal was getting approval to bring the vaccines to market as fast as possible (the prelimary approval type).
In a pandemic, it’s good to have vaccines available sooner then later. That’s a different goal then optimizing for cars looking good.