Re: Vaccine vs Covid itself
Posted: Sun Mar 21, 2021 10:08 am
Splatt wrote: ↑Sat Mar 20, 2021 1:24 amWe're not going to need boosters and it will be fine.fon wrote: ↑Fri Mar 19, 2021 1:15 pmMemory cells have to recognise the pathogen. The whole point is in 15 years time there's likely to have been enough mutation that they wont.Michael Yeadon has previously argued confidently that existing immunity is bolstered by exposure to similar corona viruses. Hence not Meaningless. And you previously forcefully stated memory cells take over from there more long term and can/will ramp up if needed.
The fact we've seem multiple immune escape variants within 6-12 months is a good indicator of that.
Or are you seriously claiming that these current vaccines, once given, will never ever need to be updated or need any form of booster?
Have you informed AstraZenica of this who have already started making one?
Because if there is need for a booster, you're entire argument about vaccinating now is utterly meaningless.
The virus is about 10,000 amino-acids long and the spike about 1000. A natural infection results in T-cells that recognize thousands of "epitopes" (little bits of the virus maybe 10 or so amino-acids long) all over it, including ~100s on the spike.
Some of those epitopes are also matched by B-cells and the antibodies that they create. During the course of an infection your immune system optimizes those antibodies to "neutralize" the virus. A neutralizing antibody is one that disables the virus just by sticking to it. There are a small number of critical places on the spike protein where this will work.
Those antibodies hang around for a few months, maybe a year, to prevent immediate reinfection. Meanwhile the virus gets to roll the dice. It's changing amino-acids at random. In maybe a year it escapes some of those key epitopes that the neutralizing antibodies are using. It's not hard because it only needs a few changes.
But it can't escape all those 100s (or even 1000s) of other epitopes in one go. So you are reinfected. But it's not "too late". You have a mild reinfection. As soon as the virus gets inside cells (which it will do) T-cells who have not forgotten all those other epitopes will recognize it, kill infected cells, and, if necessary, reboot the process of making and optimizing antibodies for the new version. You just got an update to your antivirus software. And maybe a few sniffles.
Antibodies are the kids swarming around in shiny trainers who think they're badass. They work well for a bit at doing one thing and then they're gone. T-cells are playing the long game. They're that guy with a grey beard on his rocking chair in front of his house. You may not even notice him at first. He may even look like he's dozing off at times. But he's seen it all before, he knows what to do, and his shotgun is never far away.
There was a lot of alarmist reporting last year about how antibody levels start to drop after 6 months or so. There would be no point keeping them forever because the virus mutates. It appears evolution has adapted them to stick around for just about the right amount of time that they're actually useful for.
We are already seeing this process with the B.1.135 variant:
https://www.medrxiv.org/content/10.1101 ... 21251247v1
There are two important things to note about this study. One is the enormous confidence interval, caused by its being too small. In fact to show any statistically significant efficacy the efficacy would have had to have been better than about 57%. The efficacy of the AZ vaccine is about that anyway. So this doesn't tell us the vaccine has 10% efficacy against the variant. All it really tells us is that the efficacy is less than about 60%. Which isn't surprising.
The second thing, which is much more important, is that there were no cases of severe disease or death in this study. Partial escape from neutralization is not surprising or concerning. If reinfection is severe then we have a bigger problem.
A more important follow-up study, also on B.1.135 is this one:
They tried the existing vaccine against the new variant on hamsters and confirmed two things: It does neutralizes less, but no severe lung infections were seen in the vaccinated hamsters compared to the control group. Exactly as expected. You lose full neutralization but are reinfected mildly.
Now, as for cross-immunity from other Coronaviruses, Yeadon has been criticized (reasonably) for concluding too much from the Le Bert and Grifoni studies. These were early studies that found cross-reactivity between the T-cells of people who hadn't been exposed to SARS-CoV-2 with the "novel" virus. A reasonable conclusion was that these were memory T-cells from a similar virus (perhaps one of the related "common-cold" Coronaviruses we all get infected with every few years or so). This cross-reactivity was found in about half of SARS-CoV-2 unexposed people.
But all that study showed was that some T-cells took an interest. It didn't prove anything about whether that corresponded to actual robust immunity of any kind. In theory it could even have made things worse (this can happen but is the exception rather than the rule).
But then the smoking guns started to show up. This was the most important early one:
https://www.biorxiv.org/content/10.1101 ... 414v2.full
This didn't just find cross-reactivity. It found actual neutralizing antibodies (yes, even neutralizing ones).
And even harder to argue with is this recent study:
This looked at a large sample of people who had previously been known to have an infection with a regular endemic common-cold coronavirus and compared how they got on with SARS-CoV-2.
They found the endemic coronaviruses (which they call "eCov"s in the paper) have almost no efficacy at preventing you from getting COVID-19. But they are almost as good as a vaccine at keeping you out of the ICU.
The eCoV+ as compared with the eCoV– hospitalized patients had a significantly lower odds for intensive care unit (ICU) admission (OR 0.1, 95% CI 0.0–0.7) and a trend toward lower odds of mechanical ventilation (OR 0.0, 95% CI 0.0–1.0). The odds of ICU care (OR 0.1, 95% CI 0.1–0.9) remained significantly lower in the eCoV+ as compared with the eCoV– patients after adjustment for age, sex, BMI, and DM status.
An OR ("odds-ratio") of 0.1 is essentially equivalent to a "vaccine efficacy" of 90% (you can't directly convert an OR to an RR and the reason we have an OR is this is a retrospective study, but it's close enough as makes no difference).
If cross-immunity from viruses whose nearest common ancestor with SARS-CoV-2 was hundreds or thousands of years ago is that strong, I don't think we need to worry about B.1.135 or whatever variants may be around in a few years' time.
These memory T-cells last for at least as long ago as SARS1 happened (about 17 years) and probably lifetime. There is every reason to believe that a natural Covid infection, or a vaccination, will protect you from severe disease and death basically until you're really old at which point you're just as likely to die from any of the other endemic respiratory viruses.
I am very dubious about the need to constantly keep revaccinating people with updated vaccines. This may turn out to be harmful. After adolesence your immune system has a finite system of "naive" T-cells (blanks basically-- that haven't been adapted to match anything specific). By the time you're getting old you're running low on these, which is one of the reason why relatively novel pathogens are more of a curveball.
I'm not sure I want all of mine used up through year upon year of vaccinations for slightly different versions of the same virus. I'd rather my immune memory took a more catholic view of the virosphere, with a well-balanced toolkit of memory cells corresponding to whatever viruses are out there, and a few naive T-cells in the chamber in case something new comes along.
Of course I don't know the long-term effects of constant vaccination throughout life of the young for sure. Nobody does. But if you aren't getting a clear benefit from it I wouldn't do it, as you can't assume there is no downside. Lunches are rarely free. Given that pandemic Covid wasn't even that bad (for the young and youngish) I don't think endemic Covid will be anything to go around regularly vaccinating people for.