Ask for your money back on OAS

"Original Antigenic Sin" is a stupid, misleading meme that is being renounced. If someone told you OAS is real, they were stupid.

In the wake of the bivalent boosters, yours truly went silent on the controversy that had been the animating force behind much of the writing at Unglossed in 2022 — “Original antigenic sin.”

A sudden mainstream consensus rapturously materialized declaring that the bivalents had been thwarted by “imprinting” (which is real) and “OAS” (which is not), the new shots couldn’t make new antibodies because everyone’s immune systems were already caput, and it is unproductive to rant during a fireworks show. No, nothing so electrifies a rant as the monastic silence of the studio bunker. Insert Network “mad as hell” scene youtube embed.

Now the fireworks have calmed down, and two things may be remarked upon.

One

Real-world antibody results from the bivalent shots were, in fact, equivocal. Some studies found a relatively flat response to “Omicron” (BA.4/5 spike), some a relatively high response.¹

Nannan Jiang, L. et al.

Yes, the injections pushed out to the masses on the basis of biological responses in 8 mice (lol) seemed, in the end, to do a so-so job at making blood better able to pester “Omicron” in a lab setting.

“So-so job” is hardly a devastating outcome, given that most of these studies only involved a handful of subjects, and the fact (however mystifying and stupid) that the bivalent injections literally include equal parts Omicron and Wuhan antigen, adding to 4 to 6 parts prior exposure to Wuhan. On top of the RNA quality issues that make it questionable which and how much of intact spike is actually produced in duped, unlucky recipients² (as opposed to delicious DNA plasmids³), this is hardly a cause for condemning nature’s design of the immune system rather than the idiotic humans who designed the new injections.

As always, my beef with combatting the stupid myth of “OAS” is not to defend the injections, but to defend the natural immune system. We must throw out the baby, not the bathwater.

Two

The rapturous media embrace of “Original antigenic sin” triggered by early bivalent results is predictably fading; in the wake of all the adulation and debauchery, Science™ is now entering the hangover phase.

As the first sign of shamed repentance, Ali H. Ellebedy, who has batted for multiple American flu research luminaries in the last decade, including Webby at St. Jude and Wrammert at Emory, has teamed with Marios Koutsakos to issue a repudiation of the term and of the most common (and stupid) misinterpretations it has promulgated.

pdf at cell.com

What do Koutsakos and Ellebedy have to say about “OAS,” and how does it compare to what other Covid vaccine skeptics have told you?

I have ranted for over a year that “OAS” is stupid and not real. This was offered as a counter to the position that “like, yeah, brah, obviously it’s real, because here’s a quote from the dude that invented the term in 1960 that says so, regardless of what the last 6 decades of research actually shows.” Insert substack embed to highly-shared post by role-playing medieval monks and/or cats who pretend to know anything about biology.

I have said, further, that the term itself has driven widespread confusion within the research, with many green researchers in recent decades seduced by the word “sin” into imagining and attempting to amplify conclusions not in fact offered by the term’s originator; but that obviously the fault lies with that same individual, Thomas Francis Jr, for using a misleading term.

The Mess Francis Made

What do Koutsakos and Ellebedy say, in their new manuscript? Here are the highlights:

What Koutsakos and Ellebedy say

The literature on OAS, inherently focused on influenza, is often seemingly contradictory. This results from inconsistent definitions of ‘OAS’ and different methodologies to measure what is considered OAS.

Over the last few decades, the highly equivocal use of the term ‘OAS’ and its susceptibility to misinterpretation due to connotations of the word ‘sin’ have limited its utility. It might thus be prudent to avoid the term and apply more consistently defined terminology that is less prone to misapprehension.

Think about this language. Who is misapprehending? If the word “sin” is the source of the problem, obviously it is those who imagine and suggest that the biological qualities included in the theory of OAS are detrimental, and deviant. Further, as this is a manuscript intended for institutionalized researchers, it means other scientists.

But if other scientists imagining that there is some inexorable force called “OAS” that leads to detrimental, deviant immune responses are committing misapprehension, so too are the anonymous monks and cats bombarding you with rabid illusions based on an obscure, stupid scientific myth.

Compare what those other Covid vaccine skeptical writers have said, to what I said in “The Mess Francis Made”:

What I said

[Monto, et al., in a previous rebuke of ‘OAS’ in 2017] are essentially complaining that the common modern use of the word is wrong; akin to those who would describe modern use of “ironic” as wrong. They wish to propose that almost everything currently being described as “OAS” be assigned new or different terms. But absent aggressive language-standards-enforcement by scientific journals, the phrase must by definition “mean” whatever the present writers and readers have in mind when it is used; and anyway the horse is out of the barn.

And how was it supposed to happen any other way? Were new minds somehow not going to emerge from schools and reencounter the old phrase, have it instantly conjure up a meaning akin to “exacerbates the severity of the current infection,” and launch into using it that way? How was the field supposed to be future-proofed against this mistake? (August 24, 2022)

Some more highlights from the new paper, vs. what I have said regarding “OAS”:

Timing of sample:

What Koutsakos and Ellebedy say

[T]he time of sampling post-re-exposure is also confounding, with earlier and later time points showing different extents of bias [toward first-encountered epitopes].

What I said

8.5 days (!) is too early for the arrival of novel, anti-Omicron antibodies. So can testing blood samples from 8.5 days possibly demonstrate whether novel, anti-Omicron antibodies end up being created to begin with? (No!) (February 2, 2022)

Lack of comparison to the un-“sinned”

What Koutsakos and Ellebedy say

[T]he analysis needs to include a group not exposed to A (group B), a comparator frequently missing from the literature

What I said

This leads to a third category of error; as modern studies which misapprehend the definition of “OAS” tend to take the underlying mechanism for granted, to such a degree that no attempt is made to compare new antibody responses to a non-“sinned” control group. To substantiate the claim that “prior immunity limits new responses,” you must measure against a control group with no prior immunity. In practice this almost never happens; even in animal studies (but mostly in human studies). (August 30, 2022)

No problem with pre-existing coronavirus immunity

What Koutsakos and Ellebedy say

However, there is limited evidence to suggest that [back-boosted pre-existing human coronavirus] antibodies affect the development of neutralizing antibodies against SARS-CoV-2 [in natural infection] or that they significantly modulate susceptibility to severe disease

What I said

Oh. That’s strange. Participants with high pre-existing antibodies against other coronaviruses had mild outcomes… just as often as those with low antibodies. And vice-versa. These results demonstrate that Original Antigenic Sin is actually… not real. (December 12, 2021)

Nothing actually wrong with post-“breakthrough” Omicron antibodies

What Koutsakos and Ellebedy say

In cohorts of Omicron-infected individuals of varying exposure histories, it is evident that prior exposure to the Hu-1 Spike by vaccination results in greater antibody titers to Omicron after breakthrough infection than in SARS-CoV-2 naïve individuals.

What I said

So, as a sort of “opposite-OAS,” we see here that those with more previous exposure to pre-Omicron spike and/or whole virus, mount a more robust response against BA.1 after infection (August 1, 2022)

That’s it, that’s the post

Essentially everything I have argued in my critiques of “OAS” is affirmed in the manuscript by Koutsakas and Ellebedy. Ellebedy, again, has been directly involved in much of the research regarding sequential immune responses to influenza in the decade preceding SARS-CoV-2, including the Emory school’s quixotic attempts to decipher “imprinting” in order to unlock a universal flu vaccine — he is from the fold of “OAS,” and has seen first-hand its flaws and limitations in actually describing or predicting biological reality.

Whereas the promulgators of “OAS” can offer nothing but illusion and feverish noise. They almost never even can show a comparison to the un-“sinned” when waving their charts around. They are like the cliched boys at the frat party, pulling out their guitars to play Thomas Francis’s tired, stupid chords and appear deep.

1. Example of no improvement over monovalent:

Wang, Q. et al “SARS-CoV-2 Neutralizing Antibodies After Bivalent vs. Monovalent Booster” medrxiv.org

Example of improvement over monovalent:

Nannan Jiang, L. et al. “Bivalent mRNA vaccine improves antibody-mediated neutralization of many SARS-CoV-2 Omicron lineage variants.” medrxiv.org

2. See “Myocarditis and Bolus Theory” for my lil’ thesis on RNA quality issues.

3. McKernan, K. “Pfizer and Moderna bivalent vaccines contain 20-35% expression vector and are transformation competent in E.coli.” Nepetalactone Newsletter.