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Comment by jpxw | Hacker News Reader

From AstraZeneca:

> One dosing regimen (n=2,741) showed vaccine efficacy of 90% when AZD1222 was given as a half dose, followed by a full dose at least one month apart, and another dosing regimen (n=8,895) showed 62% efficacy when given as two full doses at least one month apart. The combined analysis from both dosing regimens (n=11,636) resulted in an average efficacy of 70%. All results were statistically significant (p<=0.0001).

Also:

> and no hospitalisations or severe cases of the disease were reported in participants receiving the vaccine.

https://www.astrazeneca.com/media-centre/press-releases/2020...

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Wow, what a fascinating phenomenon. A weak first dose somehow primes the immune system better than a full one?

“The thing is, the immune system is very complicated.”

quote from the link here, but for those who don’t want to click through (this article is fascinating though), it is told in the context of a joke which i will post below the link.

https://www.theatlantic.com/health/archive/2020/08/covid-19-...

There’s a joke about immunology, which Jessica Metcalf of Princeton recently told me. An immunologist and a cardiologist are kidnapped. The kidnappers threaten to shoot one of them, but promise to spare whoever has made the greater contribution to humanity. The cardiologist says, “Well, I’ve identified drugs that have saved the lives of millions of people.” Impressed, the kidnappers turn to the immunologist. “What have you done?” they ask. The immunologist says, “The thing is, the immune system is very complicated…” And the cardiologist says, “Just shoot me now.”

IANAD but my guess is maybe a stronger immune response in the first dose makes the immune system respond so quickly to the second dose, that it doesn't have time to get anywhere and interact with enough of the body to have much of an effect. That way a weaker immunization in the first dose leaves more room for the second dose to have a refreshing/strengthening effect. Basically, 1 + 2 > 2 + 0

Sample size is too small to say that. The vaccine works across all doses, but that is all the data shows.

Is there possible explanation why would first half dose have much better results than full dose?

This vaccine is an inactive host virus whose payload has been replaced by the coronavirus "spike". It has always been a worry that the body will generate immunity to the host virus and thus make the vaccine less effective. That is a likely explanation for the first-full-dose regimen being less effective.

Shouldn't it warrant a research if even smaller dose has even higher efficiency?

Yes. But clinical trials are expensive ($100m plus) and time consuming.

If both regimens underwent Phase 2 testing, there should be data on comparative immunogenicity.

Statistical factors: the sample size is so small that it could be less effective and still show up this much more effective.

I hope not, but sadly it is a real possibility that needs further study.

One thing that isn't obvious to me is exactly how `n` is defined, and how that relates to how many people of that `n` were infected by covid during the trial. E.g. maybe n=2,741 people were vaccinated following the first dosing protocol, but perhaps only a small fraction were infected with covid. So the actual sample sizes being used to estimate the efficacy of each dosing protocol may be smaller.

Yes, they do state that all of the results are statistically significant though, with very low p-values.

And they should be accounting for double dipping as these are interim results.

https://www.cnbc.com/2020/10/21/astrazeneca-shares-slide-aft...

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