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Comment by avsteele | Hacker News Reader

There are numerous bodies of data supporting waning immunity at this point. This data is based on real-world breakthrough rates, not antibody counts.

Two examples:

1) Israel data shows high level of breakthrough infection. This is the basis for their booster policy:

https://www.reuters.com/world/middle-east/israeli-doctors-fi...

2) Moderna just released their own study showing reinfection rates at 2x at 13+ months relative to <8 months post second dose.

https://investors.modernatx.com/news-releases/news-release-d...

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Its worth noting that a 2x reinfection rate of a very,very,very small number is still a very,very,very small number. The difference between the high dose modern a approach and the low dose approach of other manufacturers seems to be pretty strongly significant, moderna appears to be working quite a lot better for longer.

It’s also important to note that for a first try, on an accelerated dosing schedule, 95% efficacy was incredible and blew all of the estimates out of the water. Falling to ‘merely’ 80% efficacy after several months and a major mutation still leaves you in a very good position.

Reinfection/breakthrough is exactly in line with what the parent poster is claiming, which is that it is due to antibodies waning naturally, either from vaccines or from natural infection. However, the B-cells remain and continue to recognize SARS-CoV-2 antigens, causing a rapid production of neutralizing antibodies within hours, as opposed to close to a week in the natural infection case. This leads to greatly reduced hospitalizations.

> There are numerous bodies of data supporting waning immunity at this point.

Why that happens is less clear though. Is it a fault of mRNA tech itself? Or the dosing schedule? 21 days is very close together for a 2 dose vaccine, most are 6 months or years apart.

Using 21 days was a good way to get the trials done fast, if they'd used 6 months we'd be where we were 5 months ago, but this was one of the risks. Canada, which spaced doses out further, isn't seeing nearly as high of a rate of breakthrough cases.

I'm not saying we can conclude definitely that dosing is the problem, but it's a question worth investigating before coming to any firm conclusions that mRNA vaccines aren't good enough.

Agree it seems likely that dosing plays a fundamental role.

Moderna while still seeming to suffer from this problem seems to be suffering less than Biontech, they are very similar in general, biggest difference is Moderna having already a longer minimum waiting period between the shots and a way bigger dose of mRNA per shot. So this may already be a hint.

Also currently it looks like a third shot is giving a really great boost compared to the second one, at least in the short term. Same with using mRNA as a booster shot after a vector based vaccine.

It’s weird that there is so little mention of natural immunity as a cause of declining measured “effectiveness”. The vaccine effectiveness should trend towards 0 as the unvaccinated population acquires natural immunity. That doesn’t mean the vaccine isn’t working.

I don't understand this mechanism. Can you elaborate? How does the unvaccinated population influence measured vaccine effectiveness?

Imagine a study where half gets vax and half doesn't. If population is pristine at outset at end of study VE is 1-ratio between people who get COVID in the two arms.

Now, if there is any prior exposure to the disease among participants (this isn't always known, esp. for something like COVID), and if there is any natural immunity that accrues, this will pull that ratio towards 1 (VE=0)

Protection from severe disease is still strong.

Probably the worst part about Covid-19 is that Sars-CoV-2 was a totally new Virus with a high attack rate, on top of the danger to the individual patient. If most of the population has seen "something like" it, even very distant variants will not be as bad.

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