Lurking Leviathans
The beast of antibody dependent enhancement has yet to come clearly into view, as the light of summer begins to fade.
Work on the Immune Equilibrium followup has taken a back seat to keeping up with this week’s various emerging developments. The following topical post is a superficial survey of some of these subjects. On the docket:
Israel Boosters Itself into Obscurity!
The “Poised to Acquire” Paper!
Does Science Even Know How to Measure IgE Antibody Levels?! (No.)
What Was in Those “Die Herd” Footnotes?!
Israel Boosters Itself into Obscurity!
Israel has gone dark again, for the moment. Although the Ministry of Health continues to post rates of test-confirmed “cases” and “serious illness” per 100k for both over 60 and under 60 years-old citizens, this can no longer be used to keep tabs on Covid vaccine “severe outcomes efficacy.” Not only has Israel aggressively booster-ed the elderly, but substantial progress has already been made among the middle-aged:
The 40-59 group is presumably the largest driver of “serious illness” (likely ongoing hospitalizations) for the under-60 cohort. Vaccinated severe illness rates continue to be much less than unvaccinated rates in the under-60 graph, despite nearly equal rates of test-confirmed infection. But if the vaccinated group’s outcomes are now being positively influenced by triple-dosing, the apparent performance on the graph no longer tells us anything about what would happen without the booster.
I remain open-minded about whether triple-dosing will, in fact, turn out to change outcomes in any meaningful way. But either way the lack of an efficacy drop (or infection enhancement) signal has now become meaningless, until the Israel dashboard clearly removes triple-dose recipients from the cohort pool (as would be reflected by adding a triple-dose outcomes rate).
I will have to acquire a better proficiency with the more poorly-presented figures from the UK for now, I suppose.
Meanwhile, other prominent Covid vaccine skeptics appear to be catching up to where I was three weeks ago,2 in agreeing that the signal for antibody dependent enhancement has not yet arrived.
Unless…
The “Poised to Acquire” Paper!
I am just as skeptical of any efforts to read the tea-leaves of antibody dependent enhancement from subjecting the blood of Covid vaccine recipients to various torturous lab interrogations, as I am of assuming triple-dosing will work in advance of evidence.
So when I read, in the introduction of the leviathan “Poised to Acquire” paper posted to pre-print on Monday, that “some [Pfizer vaccine recipient] sera lost neutralizing activity and enhanced the infectivity,” I almost did not have the motivation to wade through the 31 pages of profoundly dense results to interpret what they meant.4
I presumed that, for the portion of the study relevant to that claim, the authors were working with yet another “neutralization” trial, involving some unwieldy combination of pseudo-virons (non coronaviruses which have been forced to express the spike protein) and pseudo-cells (lab cells which have been forced to express the ACE-2 receptor) and concentrations unnecessarily displayed as “titers” (just speak English!) and statistical machinery and on and on and on, whose correlation to real-world infection results could not possibly be knowable in advance of the real-world infection results revealing themselves to us, down the road. And indeed, that is what they have done, with the added twist that the authors added changes to the current “Delta +” spike protein’s receptor binding domain that they felt were plausible based on SARS-CoV-2’s previous criminal record.5
So how could such an “infection simulation” possibly show that Covid vaccine-induced antibodies appear to “enhance” their pseudo-virus? What would they compare the results with? Unless it was worse than a control - where the test virus just has its way with the test cells - even a total failure to prevent infection compared to control at the highest concentrations is not a demonstration of enhancement. At best, I thought, the authors were being sloppy with their syntax.
I was wrong.
In the test results, the pseudo-virus infected more test cells when Covid-vaccinated samples were at a higher concentration, for all but three donors. It should always be the opposite - higher concentrations should either make no change to interference of the test virus, or improve interference.
Note that “Delta 4+” refers to the pseudo-virus which was fitted with the authors’ mutant, quadruple-edited Delta + spike protein receptor binding domain, as well as Delta’s native “NTD” - a structure in the middle of the spike protein. “Delta 4+ WT NTD” refers to the pseudo-virus created when the authors mixed and matched their mutant receptor binding domain with the much older, original NTD structure. Note also that NTD, once again, is a structure on the spike protein - it is “not to be confused” with the nucleocapsid, another hot-button topic in this realm (it is obviously to be confused; I had to rewrite this entire section because I confused it, because abbreviations are confusing).
Additionally, the value for “0” either appears to be arbitrary - the amount of measured infection of test cells for each donor at the lowest (most diluted) concentration of their particular sample - or based on a statistically determined “control” amount of infection; either way, there was a baseline which was not “total infection,” so that enhanced infection was measurable. In each subsequent plot, the concentration is made progressively higher. At the highest concentration, 10:1, most - but still not all - of the donor samples managed to save some or all test cells. But at medium-high concentrations, the donor’s antibodies are somehow helping the pseudo virus get into test cells.
The authors chose to compare a native Delta NTD pseudo-virus with a retro NTD pseudo virus for two reasons: Delta is believed to have evolved more in the NTD direction than the receptor binding domain direction to begin with, and so the changes to the NTD are what are presumed to grant Delta some of its magical “contagiousness” powers; and, some formulations of NTD-binding antibodies are believed to be capable of giving the receptor binding domain of the spike protein an accidental boost.
Snce the mRNA script Pfizer settled on was for the entire spike protein (of the Old School version of SARS-CoV-2) rather than just the receptor binding domain, it plausibly induces the production of NTD-binding antibodies; but whether they are functional or counterproductive could vary according to the whims of the recipient’s immune response.
Lastly, figure E: This is merely a plot of all donor results at the second-highest concentration, 31.6:1. But one can merely regard the graphs in figure D and observe that the pseudo-virus was more enhanced when the authors’ Future Delta RBD and Current Delta NTD were combined, compared to Future Delta RBD and “Wild Type” (original) NTD.
Because an edit to the NTD so dramatically changes outcomes, it seems plausible that NTD-affinity antibodies are instrumental.
But in what way? Both pseudo-viruses feature the same Future Delta spike protein receptor binding domain, one which the Covid vaccinated “receptor binding domain antibodies” seem only barely able to attach themselves to. Yet almost all donor samples seem to have some other, NTD-sensitive antibody that enhances infection more for the far more “novel” Delta NTD. But, how is that plausible? - if there’s an enhancing NTD antibody in these donors’ samples, one generated by a vaccine based on the “wild type” spike protein, it should be even more enhancing for a wild type NTD when equally unrecognizable receptor binding domains are employed.
Again, the study is not litigating whether evolution to the spike protein simply made donor samples incompetent at stopping the pseudo-virus. Rather, whether future changes to the receptor binding domain will make the Covid vaccine-programmed NTD antibodies more able to enhance binding. But if this were the case, the more familiar “wild type” NTD might be more “enhanced” by the vaccine-induced NTD antibodies.
What the authors propose, is that Delta is already “leaning into” convalescent NTD antibody structures from antibodies generated from prior infection (and, implicitly, vaccination) in order to boost the receptor binding domain; therefor only a competent receptor binding domain antibody can overcome this trick.
But there is a different possibility: Donor NTD-sensitive antibodies are not causing enhancement at all. They are instead helping - the samples subjected to a pseudo-virus with a more recognizable NTD, simply, did a better job inhibiting infection (it’s revealing that there was some apparent enhancement even in the mutant+wild type trials, an outcome the authors go out of their way to discount in their text).
In grasping onto the first possibility without even considering the latter, the authors rely on their extensive observations with various commercial monoclonal antibodies. The result is that the study is arguing that the Pfizer vaccine-induced NTD antibodies should be convicted entirely on the basis of their monoclonal NTD isolation tests alone. But the sera of the donors evaluated in the “neutralization” tests doesn’t consist of vaccine-induced antibodies alone. It consists of all the antibodies these individual donors have ever created in their life; some of which may be reacting to a totally different protein on the pseudo-virus envelope.6
We must ask: Was there, perhaps, some way the authors could have more concretely helped demonstrate whether vaccine-induced NTD antibodies are either “helping” or “hurting”?
Yes.
By including non-vaccinated, immune-naive individuals in their serum tests.
But as they did not do so, their results are provisionally useless.7
If an imminent strain of Delta begins to evade the original Covid-vaccinated “receptor binding domain” antibodies completely, that does not mean we will have arrived at the moment where the potential “antibody dependent enhancement clock” strikes midnight.8 For now, I stand behind my bet of 2-3 years, absent the boosters, and possibly much sooner if the boosters are rolled out en masse.9
It should be remembered, in the meantime, that advancing the narrative of rapid-onset post-vaccine antibody dependent enhancement, at this point, only serves to advance the widespread promotion of unproven triple-dosing; which itself might serve to advance the need for later fourth doses!
And I remain skeptical of all these stupid “neutralization” tests!
Does Science Even Know How to Measure IgE Antibody Levels?! (No.)
One thing that is curious about the obsession over Delta’s potential NTD-antibody-leveraging traits, is that the obsession appears to willfully ignore the other likely mechanism antibody dependent enhancement will potentially utilize: IgE mediation.
The “Poised to Acquire” “neutralization” test, in fact, has no way to even gauge the latter. This is by design: IgE sensitization is very difficult to measure, so researchers essentially do not even try, even if it is just as relevant, if not vastly more-so, to anticipating negative outcomes from vaccination.
This has been my impression for the last three months, ever since my encounter with anti-vax “crank” Vinu Arumugham’s provocative paper claiming that vaccine-induced IgE sensitization is the most plausible mechanism for the life-threatening infection outcomes to SARS-CoV-2 which are described as “severe Covid-19”.11
IgE antibodies are, as far as we can tell, primarily useful for defending against worms and protozoa who would like to turn our bodies into birthing wards. In the modern era, where we spend far too much time indoors, they additionally become responsible for allergies. But in the rare case where a zoonotic virus, such as Dengue, is introduced to the bloodstream via injection, they also become a factor not in protection but in immune dysfunction.
Just like free-floating NTD antibodies, the danger presented by IgE antibodies is that they will retain affinity in the face of antigenic drift even after functional, “neutralizing antibodies” cease to do so. (One may imagine an off-duty EMT standing back to let a retired doctor tend to an emergency happened upon in the street, except that the doctor is blind: It would be better for the doctor not to be there at all.)
The result: The IgE antibodies not only out-compete more broad-spectrum cellular and innate immune responses, but flood the infection site with cytokines released by their attached “mast cells,” triggering a cascade of inflammatory responses.
It is apparently semi-well-known that both viral infection and vaccination can lead to some measure of IgE generation. Thus, evaluating any possible difference in IgE sensitization between these two scenarios depends on actually measuring IgE. This is especially relevant, for example, in the case of a novel vaccine platform that potentially distributes spike-protein generating scripts throughout the bloodstream. So the question I have had on back-burner for the intervening three months, is: Can IgE levels even be measured?
Today, I finally devoted a few hours of research to confirm that they cannot.
IgE are considered the “least common” form of antibodies in the blood. But the "low apparent concentration" of IgE is in fact an artifact of our inability to accurately measure how much there is outside of the bloodstream. This is intuitive, because anaphylactic shock is mediated by IgE - allergic people obviously have a ton of IgE-sensitized cells throughout their bodies, even if serum levels appear low.
Instead of being in the blood, IgE primarily winds up bound to tissue cells, including mast cells but also just regular cells, especially in "surface" facing mucosal tissues like the respiratory epithelium; a little bit more is bound to B cells. Circulating IgE is just the tiny amount of residual antibody, and does not reliably correspond to tissue concentrations - unlike IgA, which spikes high in the blood and then slowly fades, but possibly as a reflection of ending up in mucosal zones. In fact, many if not all cells which express the receptors that capture IgE are capable of scaling up how many receptors they express; the upper ceiling on sensitization - how much overall “allergy” the body has - is theoretically nonexistent.
Trace amounts of circulating IgE could correspond to trace amounts of IgE-primed mast cells in respiratory and other tissues, or they could correspond to a nuclear critical mass of anaphylaxis lurking throughout the body.
So there is no accurate way to measure the end-point of vaccine-induced IgE sensitization except to wait and see if disaster strikes.
This is yet another reminder, as if one was needed, of the hazard of thinking of “immunity” only in terms of T Cells and circulating (M, G, and A) antibodies.
What Was in Those “Die Herd” Footnotes?!
I believe I have gone overboard this time, in terms of easter-egging content in the footnotes. While my heavy concentration of “B level” content into the footnotes is not strictly a gimmick designed to reward scrolling past the bottom of the main post - it also serves to streamline my essays, so that they are not crammed with every sophomorically “clever” thought that occurs to me - a game that becomes too difficult ceases to be any fun.
Thus, for any readers that wish to skip to the highlights:
Immune Equilibrium theory vs germ theory overview, and predictions.
A review of C E Gordon Smith’s stunningly moderate and sensible 1970 comments on vaccine safety.
This spoiler-guide still leaves some nuggets unrevealed.
Two Recommended Links!
“Dr. Christina Parks testimony for Michigan HB4471 on 8/19/21.” (youtube.com). Incredible.
Kennedy, R. F. Jr. and Nass, M. on the FDA pseudo-approval. As far as I have understood until this point, Comirnaty has always been the name applicable to the Pfizer-BioNTech fake vaccine, regardless of market. Yet, the FDA approval itself relies heavily on some type of distinction. Kennedy and Nass’s takedown is therefor highly relevant to the legal status of employer vaccine mandates no matter what.
It’s [Still] Not a Vaccine!
Besides bewildering, acrobatic legalese on the part of the FDA, another key flaw in any employer-mandated vaccination requirement is that the Covid “vaccines” do not meet the lay definition of vaccine - and in fact, do not meet the CDC’s own definition, either:15
Immunity: Protection from an infectious disease. If you are immune to a disease, you can be exposed to it without becoming infected.
Vaccine: A product that stimulates a person’s immune system to produce immunity to a specific disease, protecting the person from that disease.
Since the condition induced by these experimental medical interventions does not meet the CDC definition of immunity - if you are exposed to SARS-CoV-2, you are still just as likely to be infected - these interventions, including the Pfizer one by whichever name, do not meet the “official” definition of “vaccine.”
The CDC definition, last updated in 2018, once again accords with the far more relevant (from a perspective of political legitimacy) lay definition - or, at least, it used to, before the last two decades of deliberate media propaganda waging war on the traditional consensus in the service of promoting nonfunctional flu shots.16
This may be a small comfort to individuals in danger of employer termination, who will surely be ignored by their high-on-groupthink, law-breaking Nazi managers no matter how much they point out the truth. And there is no doubt that large corporations taken to court over their illegal, abusive, ethically repugnant, and Nuremberg Code-violating mandates will find little difficulty in flooding the stand with fraudulent, four-decade-experienced super-expert witnesses with cute Irish accents to spout patent medical nonsense equivocating over the obvious; but they won’t be able to change what the CDC page said at the time of their mandates.
And as discredited and fraudulent as the CDC itself is, it cannot be exceeded as an arbiter of legal definition from the standpoint of a judge.
There are no Covid vaccines. Employers cannot mandate what does not exist.
So hurry and save your screen-shots, before one of our esteemed Disease Controllers becomes aware of their oversight.
Update - September 6, 2021:
The CDC definition of “vaccine” was altered on September 1, 2021. It no longer includes a reference to “producing immunity.”
By the new definition, which does not assert that vaccines induce “immunity,” there is no coherent reason why vaccines should even be mentioned in the CDC’s discussion of the basics of “immunization” at all.
See “Midsummer Maladies.”
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Lui, Y. et al. (2021.) “The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines.” biorxiv.org
That’s totally not basically gain-of-function research or anything! Even though the resulting pseudo-virus was higher in function! The authors even say it’s not - so it’s not!
Discovering what type of pseudo-virus the authors used seems impossible from the text alone. Nor do they clearly indicate that a specific prior study details the relevant methodology.
Nonetheless, a prior study headlined by Lui does feature references to a specific pseudovirus frame: Indiana vesiculovirus (VSV). See: Lui, Y. et al. (2020.) “An infectivity-enhancing site on the SARS-CoV-2 spike protein is targeted by COVID-19 patient antibodies.” biorxiv.org
For reference, VSV:
SARS-CoV-2:
So, clearly there is no room for some other pre-existing antibody to be distorting the authors’ observations of “enhancement”!
Ah, but I forget, controls are tres passé.
Additionally, if Delta has indeed weaponized spike protein-induced anti-NTD antibodies to compensate for immune responses, so what? It is likely that this is a far more common tactic in viral “immune escape” than we think, and therefor not associable with antibody dependent enhancement after natural infection (whereas vaccination, generically, is highly associable from a bird’s eye view, regardless of mechanism).
See “Boostermania.”
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Isn’t it “funny” how that two-decade media campaign seems to have been in deliberate preparation for “something”…
/ Substack tracking scrambler link (?): Introduction to Agricultural Economics (What's New in Trades & Technology) 7th Edition (amazon.com) /