Moar Boosters Not Moar Better

It’s looking like spike tolerance builds with boosters.

A couple of posts back, Argus pointed me at this article on Unglossed

Tolerance Cometh: IgG4 After Multiple-mRNA Doses

It’s a pretty technical article covering this paper.

If you are into technical details then just go read that article and you can skip my summary. I’m not going to try and replicate what Brian has already done, but I know that sometimes I really just want someone to summarize a complicated article for me, that’s what I’m going to try to do here.

Very important caveat here is that most of this data is from Health Care Workers, and the total trial population is very small at 67 split into two independent cohorts. This is a small population and it really should be replicated at a larger scale. That said, the effect is quite strong, and it fits really well with what we are seeing currently with very high case and even hospitalization rates in the more vaccinated.

But what does it say? In a nutshell, repeated dosing with mRNA vaccines (especially 3+) generates spike tolerance, In a very similar way as allergy shots reduce symptoms of environmental allergies.

For allergens, this is great, because they are benign. Unfortunately Covid is a virus. Effectively there is a huge spike in what are called IgG4 Spike antibodies starting on or around dose 3 (getting worse with dose 4). IgG4 antibodies are apparently degenerate antibodies (they can't further evolve) and they are selected to hide what they bind to from the immune system. Again, allergies are a great example of why we would want this. If our body becomes use overreacting to something like a pollen, hiding it from the immune system is an easy way to fix that issue.

This is what the European regulators warned about, repeated boosting might lead to less immune response over time. Dr Malone has said something similar on Rogan.

A second small cohort incidentally found (it was not what they were testing for, so it's a item of interest to investigate, not a study result) that boosted individuals take more time to clear the virus.

Case rates in highly vaccinated countries are elevated. Case rates in boosted cohorts are similarly elevated. The UK data shows that shortly after dose 3 was widely available, the 3 dose cohort had much higher case rates than the 2 Dose only cohort is also coherent with this finding. Basically there is a lot of conciliance with this finding.

I wouldn't say this is a slam dunk. The largely HCW cohorts are much more likely to have regular environmental exposure to Covid which could potentially drive their tolerance. The very small populations also leave much more room for chance to play a role. I sincerely hope this is replicated and expanded and we can get a more solid understanding.

So, in summary, it looks like repeated boosting might act like an allergy shot and generator l generate immune tolerance. It's consistent with other data, but we really need to expand and replicate this study. If it stands, it would be a dagger through the heart of regular booster programs.

Let me know if you'd like other summaries or if you'd prefer just links here or on Twitter in the future. I really feel like we are starting to enter the vaccine endgame, I'm just not sure what plays are currently on the table.