ADE in monoclonals and mRNA-vaccine

FcR go brrrrrrrrr

Another day, another “forecasting” becoming truth, another many of my pieces and tweets being proved.

Reevaluation of antibody-dependent enhancement of infection in anti-SARS-CoV-2 therapeutic antibodies and mRNA-vaccine antisera using FcR- and ACE2-positive cells

I have many pieces talking about ADE, the mechanism itself, all the evidence that kept coming in the last 9 months, exploratory ones, and dozens of tweets about it (tweets are not even close to how I write my Substack, which I much prefer), this paper proved by reevaluation using their methodology how ADE happens.

And as I wrote multiple times, ADE was happening during all waves of Omicron, it had levels to it, and the non-neutralizing antibody was enhancing spread, especially after vaccination.

Here they found ADE is somewhat time-dependent and antibody level dependent, but the ADE factor which is the non-neutralizing antibodies persists for longer than the neutralizing ones. I also find it intriguing that the average time the non-neutralizing antibodies persists is close related to how the immunological shift happened, going from neutralizing to non-neutralizing, less inflammatory responses. This partially explains why the mechanism discussed in the piece below came to be.

I HIGHLY recommend (more like you must) you to read the piece below, you don’t necessarily need to understand the intricacy of what is going on, but this will be incredibly important in some of my next pieces.

Spoiler alert: GP120

The shift in mRNA elicited immunity

It was self-evident for anyone to see almost 2 years ago.

John Paul @ThingsHiddenn

Spike centric approach is wrong, just because it it's the part that enter the cell, should NOT be the sole target. Specially on SARS-2. It will backfire, sooner or later.

Bloom Lab @jbloom_lab

Finally, our results and other recent work in this area strongly suggest a priority should be to diversify epitopes targeted by antibodies in clinical development, such that the same mutations selected under immune pressure don't also escape so many clinical antibodies. (7/n)

Now here is where things get… spicy. The part I am referring to is the Th17. While we were among the first to bring to wider attention the Th17 aspects of both infection and vaccination, one man was earlier than most. In fact, one person was literally the first one on the planet to point out something related to Th17 and incidentally ADE.

Organ rejection after vaccine, Further evidence on the Th17

Source

Now I leave you with a question. Is a Th17 dominant response in the face of non-neutralizing antibodies and levels of ADE a good thing ?

I hope you have a very pleasant weekend.

Observation: In case you are worried about this, my entire stack, the pinned Things Hidden series is made to tackle this exact situation (Th17). How to minimize paradoxical in particular, one I need to rewrite and edit a bunch.

Massive appreciation to all the supporters, you enable me to do this !!!