Sadly, note that the study talked about here [1] is investigating the effect of the N501Y mutation, not the more worrying E484K mutation found in the South African 501.v2 strain that likely does escape antibody drugs and reduces neutralization by convalescent sera from past infections. [2]
For the vaccine to lose effectiveness, the mutation would have to drastically alter the spike protein of the virus.
This is effectively impossible as the virus is dependent on a functioning spike protein in order to infect cells, and the machinery involved with the mechanics of the spike are extremely delicate. Errant mutations that would cause compositional changes to the shape of the protein are almost guaranteed to cause functional failure. Using terminology, this is what we call a highly conserved area.
In both cases for the South African or UK strain, if you take a look at the areas where mutations have occurred, you’ll see that the code responsible for generating the spike protein is basically completely unaffected. This will generally hold true for any successive future strains.
Am I reading the second paper correctly when I say this was conducted on a sample size of 11, and they found that the E484K mutation had saw no reduction in neutralization in some of those subjects? I’m trying to get a better sense of the numbers involved to figure out how much credence to lend to the dangers posed by the second mutation.
Say that Pfizer were able to simulate 50 possible mutations and put all of them into a single vaccine, would there be any risk that the antibodies could interact with each other in some way that makes the vaccines less effective?
Also another scenario: say that we get yearly Covid shots that contain the latest strains, would these accumulate over the years and start interacting with each other?
An N to Y mutation is associated with tighter specificity in binding protein protein interfaces. An E to K mutation is changing the surface charge from negative to positive so it shouldn't be surprising that it reduces antibody's ability to recognize, assuming it's in the most recognized pocket. Hopefully this will be a relatively easy cut and paste into the existing vaccine cassette if it turns out to spread really widely.
The bigger question I have is when will we be ready to confidently claim that the vaccine doesn’t just prevent symptoms but also prevents spread? (Edit: at the same or nearly the same 95% rate)
I can’t see a human trial being able to show this, and contact tracing is overall so poor how long will we have to wait to not see a case that can be tracked back to a vaccinated individual before we are willing to agree that the vaccine is highly effective at stopping transmission?
For example, by Feb 1 we will have millions of people who are effectively protected at least from symptoms due to vaccine. So e.g. by March 1, if we have no, or single digit, reported cases of 2-week post-jab transmission?
The corollary is how durable is the effect?
To fully reopen the economy you need some kind of consensus on where the truth lies to these two questions.
I wonder if public health agencies will never really admit, but just the case count will start to dwindle and mitigations will start to lessen, without ever really coming out and admitting vaccinated people don’t need mitigations 2-weeks-post-jab.
Similar to how we’ve never really admitted that people who’ve had COVID are immune and can no longer spread it.
I think fundamentally gov’t is too afraid of having two classes of citizens, and mainly, that one class (the antibody negative class) lying that they are actually the other.
Reopening the economy or not is a political choice and doesn't necessarily depend on vaccine effectiveness. The economy in Florida has been pretty much open since September. We can argue about whether that is wise but the reality is they are open today.
Israel has managed to give the first shot to 20% of its population, and at this rate will be into herd immunity territory by the end of the month.
As far as pressures on healthcare systems though, once over 65s have been vaccinated (and the northern winter ends) the pressures pretty much vanish.
> Similar to how we’ve never really admitted that people who’ve had COVID are immune and can no longer spread it.
Well we don't know that. In many cases the virus reproduces and spreads without any symptoms. If the spread occurs before the immune system kicks in you could still be a carrier even though the vaccine makes your symptoms pretty much zero.
From the phase 3 trials you'd absolutely expect cases to occur after vaccinations. That's what the 95% efficacy after 2 doses means, that 5% of people had symptomatic infections.
Hopefully it is the case that the 5% are people that have a weak response to the vaccine and the remainder mostly aren't infectious. They can study this by monitoring for asymptomatic infections (I don't know if they are going to or not).
None of the data you'd need to have policies based on calculated immunity is going to come quickly, if at all.
I don't think it's reasonable to try to run an open economy for those who are likely immune and a parallel economy for those who are unknown. There's no way anyone can verify any of that in a day to day setting.
I would expect that some international borders might reduce quarantine requirements if you can show evidence of probable immunity, but not right away.
What worries me is that there doesn't seem to be some global coordination in the distribution of the vaccines. It looks more like an individual race, than a synchronized collective effort.
In the scenario where only the old accept to get vaccinated, and the vaccine doesn't reach the required threshold to stomp the virus. The virus become manageable, the economy reopen but the virus run rampant in the asymptotic population slowly mutating over-time until it finds a variant that is resistant to the vaccine by successfully infecting a vaccinated person.
And it just needs for this to happen in a large population cluster where the vaccination doesn't reach the threshold, either because they do not have access to the vaccine yet or because some fraction of the population decide to not get vaccinated, for everyone to get screwed-up again.
Maybe? The nice thing about mRNA vaccines is that the formula can be adjusted very rapidly (weeks). I feel like if there was a way to tweak the formula fast enough, we could react as fast as the different viral strains mutate. We would need to change the regulatory framework though. Having to do 3 phases of clinical trial involving tens of thousands of participants makes it hard to adapt fast enough.
It develops pharmaceutical candidates based on messenger ribonucleic acid (mRNA) for use as individualized cancer immunotherapies, as vaccines against infectious diseases and as protein replacement therapies for rare diseases, and also engineered cell therapy, novel antibodies and small molecule immunomodulators as treatment options for cancer.
While this is indeed a new vaccine modality, it doesn't change the dynamics of vaccinology appreciably. Things that were challenging vaccine targets in the past will likely remain challenging.
What I haven't seen widely discussed regarding the new variant is whether the higher infectiousness means herd immunity will be achieved later. From my amateur understanding of the SIR model, this should be the case.
So ultimately we may not achieve herd immunity except with mandatory vaccination campaigns.
There is clearly something that prevents certain people (particularly kids) from contracting COVID to the point where they will not test PCR positive even if they are heavily exposed and have not had it before.
I know several families in my town who have gotten COVID. All of these families had 2 or more kids and in 3 of the families there was at least one kid who never had any symptoms and never tested positive despite being PCR tested repeatedly.
It’s theorized that there is some cross-immunity that some people have from other coronaviruses.
Coronavirus is a generic term for a type of virus.
For example, a few of the more common strains of the common cold, representing perhaps 15% of cases, are coronavirus - but they have no real relation to _the_ coronavirus, as term is typically used.
I know some of you are following this closely and I have some questions I haven't seen any proper answer. I am hoping one of you can shine some light.
How long will the mod-RNA express the spike proteins? (where is the actual 'protein expression'/time plot?)
The poly(A) tail isn't just A (which would give a mechanic answer to my first question?), there is also a 10-nucleotide linker (GCAΨAΨGACΨ). I wonder if this could be there to trigger some sort of self-amplification. Can someone point me to the relevant paper?
Because mRNA tech for rapid vaccine development wasn't available back then and it didn't spread so far that there was political pressure for expedited trials. Now it is eradicated anyway.
The is/was several SARS vaccines. They never got to phase 3 trials, because of various problems. We learned enough from them to skip all the issues this time around.
How effective is it to use one of those molecular simulation tools to quickly calculate if the antigens created still have high affinity to bind to the mutated spike?
The problem is that we're turning this into a cat and mouse - Pfizer has nowhere near the capacity to ramp up production to make a positive impact after all.
If we enter a cycle of new variants every 9-6 months that require new vacines, simply because the volume of people infect allows the virus to have enough diversity, then it's pointless.
It's basically a "weird flex" from Pfizer, because what they should say is: even though we can make a new vaccine easily, we will have nowhere near the production capacity to make a difference, so global governments need to get their shit together.
>>> appears effective
I'm not knocking the vaccine, but that's a pretty low scientific standard.
The public is so polarized that we have crazy conspiracy theories on one side, and complete acceptance with very little questioning on the other side.
A typical drug takes about 5 years to develop and another 5-7 for clinical trials, and for good reasons. It takes time to discover side effects. This vaccine has been developed in less than a year from virus discovery to production.
I really hope this vaccine works, but I can understand the skepticism.
Why should it be not? It will be effective as long as the core protein against which the immune system response is to be triggered will remain the same.
[+] [-] alevskaya|5 years ago|reply
[1]: https://www.biorxiv.org/content/10.1101/2021.01.07.425740v1
[2]: https://www.biorxiv.org/content/10.1101/2020.12.31.425021v1
[+] [-] partingshots|5 years ago|reply
This is effectively impossible as the virus is dependent on a functioning spike protein in order to infect cells, and the machinery involved with the mechanics of the spike are extremely delicate. Errant mutations that would cause compositional changes to the shape of the protein are almost guaranteed to cause functional failure. Using terminology, this is what we call a highly conserved area.
In both cases for the South African or UK strain, if you take a look at the areas where mutations have occurred, you’ll see that the code responsible for generating the spike protein is basically completely unaffected. This will generally hold true for any successive future strains.
[+] [-] whoisburbansky|5 years ago|reply
[+] [-] mvanaltvorst|5 years ago|reply
Also another scenario: say that we get yearly Covid shots that contain the latest strains, would these accumulate over the years and start interacting with each other?
[+] [-] f430|5 years ago|reply
what does this mean in plain words? this SA variant has a totally new evasion system?
what exactly are we dealing with here? what causes it to rapidly mutate like this?
[+] [-] dnautics|5 years ago|reply
[+] [-] jb1991|5 years ago|reply
> works against a key mutation in the highly transmissible new variants of the coronavirus discovered in Britain and South Africa
[+] [-] zaroth|5 years ago|reply
I can’t see a human trial being able to show this, and contact tracing is overall so poor how long will we have to wait to not see a case that can be tracked back to a vaccinated individual before we are willing to agree that the vaccine is highly effective at stopping transmission?
For example, by Feb 1 we will have millions of people who are effectively protected at least from symptoms due to vaccine. So e.g. by March 1, if we have no, or single digit, reported cases of 2-week post-jab transmission?
The corollary is how durable is the effect?
To fully reopen the economy you need some kind of consensus on where the truth lies to these two questions.
I wonder if public health agencies will never really admit, but just the case count will start to dwindle and mitigations will start to lessen, without ever really coming out and admitting vaccinated people don’t need mitigations 2-weeks-post-jab.
Similar to how we’ve never really admitted that people who’ve had COVID are immune and can no longer spread it.
I think fundamentally gov’t is too afraid of having two classes of citizens, and mainly, that one class (the antibody negative class) lying that they are actually the other.
[+] [-] nradov|5 years ago|reply
[+] [-] iso1210|5 years ago|reply
As far as pressures on healthcare systems though, once over 65s have been vaccinated (and the northern winter ends) the pressures pretty much vanish.
> Similar to how we’ve never really admitted that people who’ve had COVID are immune and can no longer spread it.
Well we don't know that. In many cases the virus reproduces and spreads without any symptoms. If the spread occurs before the immune system kicks in you could still be a carrier even though the vaccine makes your symptoms pretty much zero.
[+] [-] maxerickson|5 years ago|reply
Hopefully it is the case that the 5% are people that have a weak response to the vaccine and the remainder mostly aren't infectious. They can study this by monitoring for asymptomatic infections (I don't know if they are going to or not).
[+] [-] toast0|5 years ago|reply
I don't think it's reasonable to try to run an open economy for those who are likely immune and a parallel economy for those who are unknown. There's no way anyone can verify any of that in a day to day setting.
I would expect that some international borders might reduce quarantine requirements if you can show evidence of probable immunity, but not right away.
[+] [-] anonytrary|5 years ago|reply
[deleted]
[+] [-] GistNoesis|5 years ago|reply
In the scenario where only the old accept to get vaccinated, and the vaccine doesn't reach the required threshold to stomp the virus. The virus become manageable, the economy reopen but the virus run rampant in the asymptotic population slowly mutating over-time until it finds a variant that is resistant to the vaccine by successfully infecting a vaccinated person.
And it just needs for this to happen in a large population cluster where the vaccination doesn't reach the threshold, either because they do not have access to the vaccine yet or because some fraction of the population decide to not get vaccinated, for everyone to get screwed-up again.
Then we get a new vaccine every year.
[+] [-] Thorentis|5 years ago|reply
[+] [-] unknown|5 years ago|reply
[deleted]
[+] [-] noncoml|5 years ago|reply
Once we are done with COVID, will the new vaccine methods enable us to develop vaccines for virus that we couldn't do before. E.g. maybe HIV?
[+] [-] tachyonbeam|5 years ago|reply
[+] [-] kdps|5 years ago|reply
From https://en.wikipedia.org/wiki/BioNTech:
It develops pharmaceutical candidates based on messenger ribonucleic acid (mRNA) for use as individualized cancer immunotherapies, as vaccines against infectious diseases and as protein replacement therapies for rare diseases, and also engineered cell therapy, novel antibodies and small molecule immunomodulators as treatment options for cancer.
[+] [-] jojobas|5 years ago|reply
[+] [-] lvs|5 years ago|reply
[+] [-] phreeza|5 years ago|reply
So ultimately we may not achieve herd immunity except with mandatory vaccination campaigns.
[+] [-] qwerty456127|5 years ago|reply
[+] [-] zaroth|5 years ago|reply
I know several families in my town who have gotten COVID. All of these families had 2 or more kids and in 3 of the families there was at least one kid who never had any symptoms and never tested positive despite being PCR tested repeatedly.
It’s theorized that there is some cross-immunity that some people have from other coronaviruses.
[+] [-] TylerE|5 years ago|reply
Coronavirus is a generic term for a type of virus.
For example, a few of the more common strains of the common cold, representing perhaps 15% of cases, are coronavirus - but they have no real relation to _the_ coronavirus, as term is typically used.
[+] [-] bpodgursky|5 years ago|reply
[+] [-] unknown|5 years ago|reply
[deleted]
[+] [-] jakub_jo|5 years ago|reply
[+] [-] mseidl|5 years ago|reply
[+] [-] anonthinker|5 years ago|reply
How long will the mod-RNA express the spike proteins? (where is the actual 'protein expression'/time plot?)
The poly(A) tail isn't just A (which would give a mechanic answer to my first question?), there is also a 10-nucleotide linker (GCAΨAΨGACΨ). I wonder if this could be there to trigger some sort of self-amplification. Can someone point me to the relevant paper?
[+] [-] zelly|5 years ago|reply
[+] [-] hobofan|5 years ago|reply
[+] [-] QuesnayJr|5 years ago|reply
[+] [-] CorrectHorseBat|5 years ago|reply
[+] [-] bluGill|5 years ago|reply
[+] [-] bagacrap|5 years ago|reply
[+] [-] m3kw9|5 years ago|reply
[+] [-] jonplackett|5 years ago|reply
Anyone know how long it would take AstraZeneca with a more traditional vaccine?
[+] [-] libertine|5 years ago|reply
If we enter a cycle of new variants every 9-6 months that require new vacines, simply because the volume of people infect allows the virus to have enough diversity, then it's pointless.
It's basically a "weird flex" from Pfizer, because what they should say is: even though we can make a new vaccine easily, we will have nowhere near the production capacity to make a difference, so global governments need to get their shit together.
[+] [-] phreeza|5 years ago|reply
[+] [-] jerzyt|5 years ago|reply
[+] [-] johndoe42377|5 years ago|reply
[+] [-] Capira|5 years ago|reply
[+] [-] luikore|5 years ago|reply
[+] [-] jimbokun|5 years ago|reply
[+] [-] UltimateBallR|5 years ago|reply
[+] [-] 7OVO7|5 years ago|reply
[+] [-] iridium_core|5 years ago|reply
Or is it simply genetic drift?
[+] [-] TexasfoldsEm|5 years ago|reply
[deleted]
[+] [-] williesleg|5 years ago|reply
[deleted]