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A couple of random thoughts. Mu and Delta were the first two variants that showed any significant change in the conformation of the spike protein that might cause problems for the "neutralizing" IgG created by the mRNA and adenovirus-vector rDNA vaccines. That was what raised the interest of the WMO. Although I should be paying more attention to international surveillance, I've got this odd limit on time, since i'm not embedded in a department or research group, so I've focused on the US, and for the most part, CONUS, looking at Alaska and Hawaii when needed...
Delta has shown us some nasty tricks. It produces more viral replication product (particles) per cycle than WHU-1 or Beta, for instance, and the minor changes in the S1 protein allow it to show more affinity for the ACE2 receptor. Mu shared some of these properties but not at the same level as Delta, hence, in my mind, its lower competitive advantage overall. Were we to solely look at the S1 conformation changes in Mu, we'd have expected its resistance to our antibodies to be a bigger advantage, but there are so many factors to consider here, sometimes the obvious fails to win.
The research I've read shows the current vaccines are adequately effective against Delta. Their efficacy against Mu would require more available virus, and clinical observation with adequate genomic testing would be simpler than an in vitro estimation of efficacy. That didn't work out.
As to whether we need a Delta-specific booster... I currently don't think so (but like so many other things in this pandemic, I might have to change my mind). At least in the US, and other countries where Delta's predominated, it's burned through the susceptible population virtually unimpeded, because so many who acquired this strain were unvaccinated, and didn't really believe in either the virus overall, or the use of NPIs for mitigation. The sharp upward trajectory, short time at peak and sharp downward trajectory are what I learned in school as the shape of a "normal" pandemic where nothing is, or can be done to mitigate its spread.
I've said earlier that I have little faith in immunity conferred by infection providing any longer, or better protection than immune response conferred by the vaccines. The "why" is that the infection-conferred immunity tends to be more specific to the variant you've contracted, and there's some serial evaluations of humeral immunity that suggest its duration is shorter than the vaccine-conferred humeral immunity. Activation and training of the cellular immune system is also interesting as there are a couple of papers suggesting that cellular immunity training and activation by naturally conferred response is much more variable than that initiated by the vaccines.
I propose this is because infection-conferred immunity has the entire spectrum of antigenic triggers from a particular strain and may in fact train IgG to look for a more complete component, where the vaccines provide triggers for fragments of proteins, which allow less-specific response, but a response more tailored to the spike and plasmid capsule of this species of coronavirus... so is likely more effective overall.
What this suggests to me, today, pending more research, and likely another wave of cases down the road, is that the current set of vaccines authorized or approved in the US today are effective as they are.
Most likely, we don't still have a lot of unvaccinated, Delta-susceptible individuals left. Part of the reason is, I'm convinced (again... as of today at 0715) that recent prior infection likely confers some protection for at least 90 and as long as 180 days against the general SARS-CoV-2 virus regardless of which variant lineage it claims. As a result, I think we're looking at 4-6 month of relative quiet, when, hopefully, all our holdouts will get vaccinated and Merck and others will get their COVID-specific antivirals out to clinical availability. And then, I expect we'll see anther wave, caused by a variant imported via air transport from a part of the world still serving as an incubator for new variants because they're inadequately vaccinated. And the public will have already told us that, to them, the pandemic's over.
My thoughts, so there's no one else to blame organizationally...
So, if the vax works better against Delta than Mu, you might expect Mu to have a fitness advantage in vaxxed folk. But, with so many people being vaxxed, the prevalence of Mu hasn't increased. Am I thinking about this correctly?
We know the flu vaccine gets updated every year to account for new variants. Does the flu vaccine repeatedly go through efficacy studies & a whole new approval process every single year (as you described above in #3 would be needed for a vaccine for the Delta variant)?
Hi, Dr. Jetelina. Would you be able to address boosters for children 12+? I haven't heard a thing about whether it's anticipated or recommended. It's my understanding that the FDA approved Pfizer boosters only for people 18+, but why is that? I believe the initial data showed that teenagers had higher efficacy than older people, but I assume immunity would wane in kids just like it does in adults over time. Could you speak to this a bit? Thank you!
Do pregnant women count as immunocompromised and "high risk" to warrant a booster? I've seen the CDC recommending shots for other high risk people, but no mention of pregnant women.
A couple of random thoughts. Mu and Delta were the first two variants that showed any significant change in the conformation of the spike protein that might cause problems for the "neutralizing" IgG created by the mRNA and adenovirus-vector rDNA vaccines. That was what raised the interest of the WMO. Although I should be paying more attention to international surveillance, I've got this odd limit on time, since i'm not embedded in a department or research group, so I've focused on the US, and for the most part, CONUS, looking at Alaska and Hawaii when needed...
Delta has shown us some nasty tricks. It produces more viral replication product (particles) per cycle than WHU-1 or Beta, for instance, and the minor changes in the S1 protein allow it to show more affinity for the ACE2 receptor. Mu shared some of these properties but not at the same level as Delta, hence, in my mind, its lower competitive advantage overall. Were we to solely look at the S1 conformation changes in Mu, we'd have expected its resistance to our antibodies to be a bigger advantage, but there are so many factors to consider here, sometimes the obvious fails to win.
The research I've read shows the current vaccines are adequately effective against Delta. Their efficacy against Mu would require more available virus, and clinical observation with adequate genomic testing would be simpler than an in vitro estimation of efficacy. That didn't work out.
As to whether we need a Delta-specific booster... I currently don't think so (but like so many other things in this pandemic, I might have to change my mind). At least in the US, and other countries where Delta's predominated, it's burned through the susceptible population virtually unimpeded, because so many who acquired this strain were unvaccinated, and didn't really believe in either the virus overall, or the use of NPIs for mitigation. The sharp upward trajectory, short time at peak and sharp downward trajectory are what I learned in school as the shape of a "normal" pandemic where nothing is, or can be done to mitigate its spread.
I've said earlier that I have little faith in immunity conferred by infection providing any longer, or better protection than immune response conferred by the vaccines. The "why" is that the infection-conferred immunity tends to be more specific to the variant you've contracted, and there's some serial evaluations of humeral immunity that suggest its duration is shorter than the vaccine-conferred humeral immunity. Activation and training of the cellular immune system is also interesting as there are a couple of papers suggesting that cellular immunity training and activation by naturally conferred response is much more variable than that initiated by the vaccines.
I propose this is because infection-conferred immunity has the entire spectrum of antigenic triggers from a particular strain and may in fact train IgG to look for a more complete component, where the vaccines provide triggers for fragments of proteins, which allow less-specific response, but a response more tailored to the spike and plasmid capsule of this species of coronavirus... so is likely more effective overall.
What this suggests to me, today, pending more research, and likely another wave of cases down the road, is that the current set of vaccines authorized or approved in the US today are effective as they are.
Most likely, we don't still have a lot of unvaccinated, Delta-susceptible individuals left. Part of the reason is, I'm convinced (again... as of today at 0715) that recent prior infection likely confers some protection for at least 90 and as long as 180 days against the general SARS-CoV-2 virus regardless of which variant lineage it claims. As a result, I think we're looking at 4-6 month of relative quiet, when, hopefully, all our holdouts will get vaccinated and Merck and others will get their COVID-specific antivirals out to clinical availability. And then, I expect we'll see anther wave, caused by a variant imported via air transport from a part of the world still serving as an incubator for new variants because they're inadequately vaccinated. And the public will have already told us that, to them, the pandemic's over.
My thoughts, so there's no one else to blame organizationally...
So, if the vax works better against Delta than Mu, you might expect Mu to have a fitness advantage in vaxxed folk. But, with so many people being vaxxed, the prevalence of Mu hasn't increased. Am I thinking about this correctly?
We know the flu vaccine gets updated every year to account for new variants. Does the flu vaccine repeatedly go through efficacy studies & a whole new approval process every single year (as you described above in #3 would be needed for a vaccine for the Delta variant)?
Hi, Dr. Jetelina. Would you be able to address boosters for children 12+? I haven't heard a thing about whether it's anticipated or recommended. It's my understanding that the FDA approved Pfizer boosters only for people 18+, but why is that? I believe the initial data showed that teenagers had higher efficacy than older people, but I assume immunity would wane in kids just like it does in adults over time. Could you speak to this a bit? Thank you!
So if we got Moderna we should ask for a booster? The messages are confusing.
What is mutational fitness? Could you talk about how that is measured and what it means? Thanks
Should people living in the household of someone high risk also get the booster?
Do pregnant women count as immunocompromised and "high risk" to warrant a booster? I've seen the CDC recommending shots for other high risk people, but no mention of pregnant women.