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Comment by sjg007 | Hacker News Reader

It’s dose. So you get a higher dose the longer you are exposed. A smaller dose infected less cells are initially infected and maybe you get less sick. Higher dose may mean you get more sick.

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Does it not logically follow that if the dose can be precisely controlled, it could help your body start developing antibodies sooner?

That's the idea behind "variolation", which was used before there were vaccines. It's risky, since you might get infected anyway, or perhaps the dose isn't enough to work.

Making strong guarantees that people will become immune and won't be infected is part of what makes coming up with a vaccine hard. It's apparently pretty easy and quick to come up with vaccine candidates.

With variolation it was not lower dose, but different (mild) strain (cowpox), which offers cross-immunity to smallpox.

It was a controlled infection with Smallpox, by scraping the skin with pus or scab powder from an infected person. Cowpox is what makes the smallpox vaccine.

You are right.

If we have a vaccine candidate that is safe, is there any reason not to give it in mass before knowing if it works? The only thing I can come up with is it takes longer to prove safety than effectiveness, but I don't much about this.

> If we have a vaccine candidate that is safe, is there any reason not to give it in mass before knowing if it works?

Yes. In some cases, the wrong kind of immune response can cause antibody-dependent enhancement (https://en.wikipedia.org/wiki/Antibody-dependent_enhancement), where the immune reaction enhances the severity of the virus.

This is not terribly common, but alas this exact mechanism has been seen in earlier work on SARS.

Also, during the H1N1 scare a vaccine used in Europe caused some people to develop narcolepsy (though perhaps more would have gotten it from the virus itself without a vaccine). It can be hard to determine that something is “safe” quickly.

SARS-CoV-2 is also at a really awkward point in the fatality curve (with the best estimate of the IFR being around 1%) that you really want to do something, but you also can't really accept a significant chance of that something having a significant side effect.

Dosing is a thing. There are high dose and low dose influenza vaccines for example. But even then immunity isn't guaranteed, you need neutralizing antibodies to develop as well. Lots of things have to go right to get a sustained safe and effective response which is why vaccines take so long to develop.

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