New data on mRNA booster vs antibody, bigger dose works better

[EPguy]

Moderna just came out with booster data and Pfizer did so recently. These data on mRNA boosters show that more is better by the criteria tested. Also there is a consistency between Pf and Moderna. For both Pfizer and Moderna, a higher 3rd/booster dose proportionately gave a higher antibody jump.

investors.modernatx.com/new...

pfizer.com/news/press-relea...

Pfizer at 30mcg= 25 X antibody jump

Moderna at 50 = 37 X

Moderna at 100 = 83 X

Assuming these are in fact comparable, in arbitrary units of X/dose it’s 0.83, 0.74, and 0.83. So Pfizer’s dose effect ratio is identical to the higher Mod dose and all are in a similar range. Among other things it supports the common thought that Pfizer and Mod are quite similar.

Antibody jump is relevant in this from NIH:

nih.gov/news-events/nih-res...

<<The protection conferred by the vaccine increased as levels of these antibodies increased>>

Most of us want the best response to pad our immune condition. So this is good support in my opinion for seeking the high (100mcg) Moderna dose if allowed, and a clear trade off as the dose decreases.

Some related side notes:

Moderna's current vax is good against Omicron. They are testing two variant (multivalent) modified vaxes, but Moderna feels the current vax is good enough, being capable of the same antibody boost even while lacking the extra mutations.

cancertherapyadvisor.com/ho...

and Moderna link above:

<<The mRNA-1273.211 vaccine includes several mutations present in the Omicron variant and is being studied at both the 50µg (N=300) and 100µg (N=584) dose levels.

The second candidate, mRNA-1273.213, includes mutations present in the Omicron variant that were also seen in the Beta and Delta variants.>>

<<The multivalent candidates boosted Omicron specific neutralizing antibody levels to similarly high levels (vs the current vax) at both the 50 µg and 100 µg levels.>>

<<Based on the strength of neutralizing titers generated by mRNA-1273 (current vax) … the Company will focus its near-term efforts to address Omicron on the mRNA-1273 booster>>

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Pfizer vs T-cells for Omicron

See link above, 3rd dose is worth it:

<<(for two Pf doses) 80% of epitopes in the spike protein recognized by CD8+ T cells are not affected by the mutations in the Omicron variant>> This could be why we're seeing good results so far in the real world on Omicron vs severe disease. But

<<A third (Pf) dose also strongly increases CD8+ T cell levels against multiple spike protein epitopes which are considered to correlate with the protection against severe disease. Compared to the wild-type virus, the vast majority of these epitopes remain unchanged in the Omicron spike variant.>>

T-cells are associated with durable (but still uncertain) protection. So we really want all three doses for best odds of durable protection. It's reasonable that Moderna has similar or better results but I don't know of any data.

[Magentas]

Great, thanks for sharing, I am receiving my 3rd dose after New Year so needed to make time to research this, so thanks for saving me the trouble and Happy holidays!

[Magentas]

Do you know anything about it taking 60 days after the 3rd dose of an mRNA vax before it reaches its highest efficacy? I understood it was 2 weeks with 2nd dose.

[souplover]

Yes, this is helpful. But I'm still not sure why the CDC is recommending a booster and not a fourth full shot. Is there a downside?

For example, what I've read so far is that the downside to getting a fourth shot too early is that it could possibly over tax the immune system. (And also might take away vaccines from the unvaccinated, but that seems less of an issue, given that vaccines are going to waste because of resistance to taking the vaccines)

[EPguy in reply to souplover]

I think you note two separate issues, dose size/name, and dose spacing.

If you get the Pfizer there is no diff in the size of the shot. But for Moderna it is a relevant question if you want the most possible. My take is immune comps are up to speed with our full "3rd extra dose" and after that we go to the standard public schedule for any further shots. Why is a good question.

For shot spacing, too close together does not give as good immune response all other things equal. There was early info on the better responses from UK where where the two first shots were spaced much farther apart than in US to conserve vaxes. How close is too close is the current question. Many countries are tightening this period in the effort to outrun the virus.

[souplover]

Thanks! It is confusing. I've decided to wait, as the CDC recommends, six months from the last primary shot. I guess I'll ask for the booster, not a fourth full (Moderna) shot, since that's what the CDC is recommending.

It's clear that the researchers are still trying to figure all this out as they go - and even so, we are incredibly lucky to have the vaccines at all.