How is it mechanistically possible that the jab has negative efficacy for transmission yet somehow appears to do something with respect to hospitalization and death?
Suppressed innate immunity means the "door" is left open. Pre-existing memory b-cells that ramp up anti-spike antibodies means the vault is locked up - viremia is blocked and so the virus doesn't spread to other organs. This doesn't work on the other "side" of the cells that are shedding the virus - i.e., into the airway. The tradeoff is still very much a net negative for most people since they were not at risk from severe outcomes anyway (and the data on "long covid efficacy" seems ambivalent).
I really appreciate detailed footnotes and references.
Some random questions that I hope will be explored further:
1. What does "trained" innate immunity really mean? To me it really can only work if you are exposed to small amounts of virus/bacteria. Just enough that your immune system can handle it.
2. Sometimes I am puzzled by claims about how good children's innate immune system is.
Is it really? Aren't kids sick all the time? Come beginning of school year and until the end of
flu season, children were the biggest vector of spread of colds/flu.
3. I am still confused by "asymptomatic". And the fact that "experts" cannot definitively answer
questions, it only means that a) they don't know or b) science is not settled.
So, you are infected, but you are asymptomatic. What does that mean? Did your natural innate immunity stop the virus in time? If yes, then the adaptive immune system wasn't even engaged and therefore no specific antibodies (and further down memory cells) were generated.
Has this been cleared up? I haven't seen any compelling papers discussing this.
4. What happens if you are vaccinated and then you get infected? Do you actually develop
any long term immunity? Or vaccinal antibodies completely prevent you from developing
any sort of robust immunity (as you would if you weren't vaccinated)?
5. It seems that Omicron is the end of the line. There have been some reports that after Omicron infection there appears to be immunity against other variants as well. So, my interpretation is the following:
a. Boosters won't have any effect: either in positive sense (Omicron largely evades it) or negative (no extra evolutionary pressure since Omicron can already evade it)
b. If getting Omicron develops long-term immunity (despite being vaccinated), it means this
is the best-case scenario. By end of the spring, we'll all either get it or be exposed to it
that fairly robust herd immunity should emerge.
Where is the flaw in this logic?
6. Omicron appears mild (to me, this is the first time in the pandemic where number of
cases and hospitalizations/deaths is clearly decoupled) at the moment. What is the
evolutionary environment where another variant emerges that is as infectious *and* more virulent? From evolutionary perspective, more virulent virus would have hard time becoming dominant (it of course can emerge, but it wouldn't become dominant if equally infectious
1. That's a doozy. On a theoretical level the question centers on whether innate immunity (Pattern Recognition -based cellular response and B-1 Cell-created Natural Antibodies) has a truly "innate" programming or whether it is, itself, a malleable pattern recognition machine (like adaptive immunity). It's seemingly a largely ignored subject, but here is a very comprehensive review of the evidence supporting the malleable model and theories how it would work: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6986364/ Also, the research trope that the microbiome promotes overall immune function (https://pubmed.ncbi.nlm.nih.gov/15158604/ - this was an exciting frontier 10 years ago, but research seems to have dried up after 2013) would seem to argue for a need to feed the innate immune system some sort of real-life input to preserve its understanding of what given patterns *mean*, in my intuition. It must learn the language and also keep speaking it, or lose fluency. Thank you for that prompt because I forgot I had that first link. Anyway, I am still not aware of any mention of "training" Natural Antibodies as GvW alludes to.
2. Children are operating without a full repertoire of antibodies, so it make sense for them to get sick a lot as they "collect them all" (though, I rarely got sick as a child myself, perhaps thanks to being in very low-hygiene environments). But on the flip side, the fact that the common cold doesn't kill them is a demonstration of innate immune competence and there was no reason not to expect that competence to apply to a "novel" coronavirus, and indeed it proved to do so. That said, the evolutionary biology perspective might argue for a more ambivalent take - it seems implausible that the immune system was built to handle what modern human life puts it through, i.e. encounter every compatible virus in the planet as opposed to the locally popular set. So I try not to go too far with assumptions about what "normal" is for childhood immune competence. I don't know if there is actual research support for childhood transmission of flu, would be keen on seeing a paper if there's one.
3. The traditional definition of "infection" is as an explanation for resulting disease. Asymptomatic infection is just that explanation without the disease. Now that we know we're all giant space-ships full of trillions of bacteria and our own cells side by side, there's plenty of budget for viruses to replicate inside the space ship and move on without disease, with spread to the rest of the space-ship blunted by innate immunity. Where we define the boundary of "infection" becomes a bit arbitrary at that point, but the accidental boundary used for SARS-CoV-2 - PCR positive test or detectable antibodies - turned out to be a very good correlate for durable immunity (as defined by lower likelihood of meeting the boundary again)! Omicron may be blurring the correlation, it was bound to happen eventually. The earliest-known example of a virus that produces common, real-life asymptomatic infection might be polio.
4. That's the big question, as acknowledged in Footnote 14.
5a,b pretty much my thinking on the subjects. Whether boosters would even add escape pressure to Delta was always a hypothetical to begin with (maybe you could argue that they are giving Omicron an edge, but the example of South Africa already serves as a negative control against that hypothesis). As far as "herd immunity," I don't think it will ever be a meaningful term RE coronavirus or flu. The design of natural immunity is to promote their sustained cohabitation with their host (us) (see https://unglossed.substack.com/p/die-herd).
6. I confess epistemic helplessness on this question. Various folks claim various understood reasons for why the SARS-CoV-2 spike was pathogenic - such as, previous priming that creates an inflammatory / IgE response against epitopes on the spike (reinforcing the superiority of innate / non-trained immunity), or epitopes that prompt autoimmunity, or something about Strep toxin - and I would assume Omicron has dropped the relevant epitopes while preserving the core function against ACE2. But then still others say it's the temperature tropism change.
The difference between ''inoculated'' and congenital immunity is equivalent to a package vacationer posing as a native speaker in the country of the body, so to speak.
Ah, it's sentences like these that make my days more shiny and liveable:
''No wonder modern medicine’s fixation on detectable serum antibody - induced via vaccination - has been a perpetual, Quixotic campaign targeting the wrong dragons.''
Well, "airborne HIV" certainly wouldn't be pleasant. On the other hand it's a niche that has turned out to be occupied by other viruses, upturning the entire logic of HIV / AIDS (and apparently the new Kennedy book is persuasive that there was never a solid reason to believe that logic in the first place) - for example, Measles goes to town on immune cells https://en.wikipedia.org/wiki/Measles_morbillivirus#Infection - "airborne HIV" already exists, in other words. So the question of what it even means for any virus to exploit immune cell receptors is another giant unknown in science.
I have read so many pages of a number of immunology books and this is the first time I ever have heard of "natural antibodies". Roitt's doesn't mention them until page 302.
"The ideal spectrum of epitopes for antibody targeting cannot be created; the immune system must focus exclusively on the spike and may target host-homologous epitopes that otherwise would not have been “of notice,” leading to autoimmune antibodies. The spike protein is a smorgasbord of such potential epitopes."
Oh yeah. They used pseudoiridine, which can apparently lead to stop codons failing.
As well as to novel frame reads / jumps, but that was already possible - normally the ORF for the spike protein, during viral infection, is being read in concert with other RNA machinery that can influence ribosomal read behavior. The 2012 paper is crazy - https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3381908/ - I never heard of anyone tricking nuclear RNP to perform a targeted nucleotide swap. Their methods are epic poem length.
Wow. This was a fantastic read. It drives home the point that for all of the advances in medicine, we essentially are throwing a monkey-wrench into a highly complex system in order to loosen one stuck gear and not giving consideration to where the wrench may end up and what damage it may inadvertently cause along the way.
I suppose now if this becomes a noticeable enough problem the solution will be to simply "upregulate" the suppressed immunity in some way via the development of a new, proprietary expensive drug that you then have to take within X days of your fifth/eighth/fourteenth/[insert number here] booster shot. Never mind what inadvertent effects this new "innate booster" drug will cause as there will be a fix for that too in time.
Thank you. Yes, everything discovered in immunology for the last 60 years has been refuting the ideas that are still the premise of vaccine development today. And yet the childhood schedule now has about one "wrench" for every one of those years of discovery.
"This new study confirms, again, that these groups are night and day in their protection against infection"
is that confirmed? Or is it protection against symptoms of infection, an easily confused metric unless they are tested directly for infective particles?
Excluding PCR testing, the only meaningful distinction between infection and not infection are symptoms, immune response, and the rarer metric of viral cultures. https://www.medrxiv.org/content/10.1101/2021.08.30.21262701v1 Combines PCR positives with viral cultures and symptoms among "early" breakthrough infections and finds much less association between the latter and the other two. So even if you screened the (recently only!) Covid vaccinated, the rate of "infection" per positive test would not be as high
I could also bandy my take on the Sweden study which accidentally turned into a giant "events coincidentally happening after PCR positives" study and suggests that "false positive deaths" - deaths "with" SARS-CoV-2 - clearly show an increased trend, implying that they were lower before (due to the early period of efficacy against PCR positivity) - https://unglossed.substack.com/p/forever-spike-v11#footnote-anchor-4 - so there was "something to lose."
2. probably jabbed in high viral load/dose traffic locales
3. human, and unlikely to retain the "I am not vaccinated [sic] until 14 days time" info in their "jabbed = freedom" minds...
I would seriously love to see the stats of that 1-14 day post jab VE rate and the impact in general on cases, etc. It almost feels like cheating to exclude that period of time.
It could well be that prior memory cells or existing Ab would prevent the needed innate response.
The survey article linked below talks about the relationship between innate and adaptive immune response to SARS-CoV-2, and notes that failure to mount an appropriate innate response prevents the development of a T-Cell response and predicts more severe or fatal illness.
"In an idealized example of a generic viral infection, the innate immune system rapidly recognizes the infection and triggers the “alarm bells” of type I IFN expression and related molecules (Weaver and Murphy, 2016) (Figure 2 A). This can occur within a couple of hours of infection. The innate immune response serves three main purposes: (1) restriction of viral replication within infected cells, (2) creation of an antiviral state in the local tissue environment, including recruitment of effector cells of the innate immune system, and (3) priming the adaptive immune response. The first two activities of the innate immune system slow down the viral replication and spread. The third is a critical requirement of the innate immune system to trigger the adaptive immune response."
And very interesting study, I hadn't encountered the suggestion that SARS-CoV-2 is already intrinsically suppressing innate immunity before, rather than the opposite - more inflammation predicts more severe disease, though not perfectly. I will be reading this. In https://www.science.org/doi/10.1126/sciadv.abj5629 Figure 2b high IFN still predicts severe outcomes (though there are some notable low-IFN-having Red squares in the middle group). But this could still be a "too much, too late" effect. Everything is relative when it comes to immune signaling.
Re: Footnote 1, I find repetition helps me with comprehension and retention, so I appreciate your persistence with any of your topics, especially for the complexities of immune responses. Exercise makes most things better.
But it occurs to me that just as some people comprehend quicker and retain longer, so do people have varying immune competence. Discussions like this one seem to describe how these activities are supposed to perform, but apparently some people perform better than others. Perhaps the key to solving this is determining why some people have poor outcomes while (most?) others are more successful, though still with varying difficulty. If we can figure out what makes the successful people perform better, maybe we can help the weaklings adjust themselves.
I'm currently experimenting with keto diet, using Saladino's Carnivore Code as a guide. His book is extensively researched, with about 700 citations of published research. His theories are based on LDL being a principal transport for delivering immune cells and excreting the waste from successful engagements. LDL reduction is an obsessive target for cardiologists particularly, and doctors generally, which might account for the observations of cardiac conditions being a co-morbidity. He cites studies that show improved immunity in people with higher LDL levels. Mine is high enough to cause mild panic in my doctors, but my experience during the pandemic has been so successful, I wonder if my high LDL is indeed protective, and all those statins my friends gorge on are actually increasing their risk.
Maybe it is not about ''more successful'' and ''poor'' at all, but simply about a most diverse interplay of diversities, which however all have the same ''intention'', namely to strive for an equilibrium, in order not to reach this as long as possible. Life is more than ''black'' and ''white'', more than ''0'' and ''1''. Without death worth living for life becomes a mere machine.
Or let me put it differently: Health is the slowest form of death for each individual living being, but disease is the fastest way for life itself to remain healthy. Therefore ''poor-ness'' is necessary for being ''more successful'' and each individual has its own pace and an individual range thereof.
People have different reasons for living, I suppose. Seems irrational to me to accept failure. Science is on the verge of substantially extending lifespans. People alive today will live as long as they want to. I'm going for the record.
Fascinating about the LDL. I have also been on the keto diet for several years now and I feel better on it than eating any other way. My own cholesterol readings, especially my LDL, have virtually always been what doctors deem too high, but I've firmly refused statins. On a keto diet my LDL went down a bit, but not hugely. I had a special cholesterol test done to determine LDL pattern type (fluffy or dense), and learned I have the desirable type A fluffy particle type. Fortunately, once I found that out my doctor stopped bugging me to go on statins. I'm 72, husband is 74 (and both of us have nearly identical cholesterol readings as our diets are the same). We're both slim, totally healthy, take no meds, and have not had flu or anything else for years. So I'm now intrigued by Saladino's theories on LDL. Perhaps they are correct! As for Covid, we've been around a number of people in the last 2 years who got it, but we've never gotten sick. We don't indulge in the silly testing games to check for any kind of positivity.
I went to keto after 2 years vegan, which cured most of my heart symptoms but HDL stayed low, TGL, TC, LDL high and started getting signs of afib. Saladino keto boosted HDL, chopped TGL, ekg consistently normal, but LDL and TC stayed high (though higher "fluffy" particles). Saladino says no problem, I'm continuing the experiment under watchful eye of cardiologist. Chapter 11 focuses on cardiac issues, which has 135 citations. The most directly relevant ref for immunity is an International Journal of Epidemiology article you can find at https://academic.oup.com/ije/article/26/6/1191/676876. There's a link to a pdf on that page with a very long url.
I've also experimented with diet and read Saladinos book (and listened to 100s of podcasts on the topic). Saladino now recommends not being in ketosis long term. He eats meat, fruit and honey. I experimented with that mainly for hand eczema. My skin was amazing after a month of meat and honey. Dave Feldman does interesting work on cholesterol also over at cholesterolcode.com
I have some fruit in season but I keep my carbs to about 5% and especially cautious of sugars due to alzheimers gene. We're complex organisms and all unique in many ways. I like frequent tests to keep close watch on my chemistry and consult several docs to try to keep the best balance. Thx for the link.
LDLs are obviously an essential molecule. I think throughput is what is important - they should be readily available, but also frequently called. This cannot be achieved by "reducing" LDLs, but does still imply that something is out of balance if the measurable levels are high. You may still accrue the positive, but risk the negative. My intuition is that it is the biological universality of double-edged swords like these which explain why a single day without exercise can take (arbitrary example) three days of exercise to compensate for.
Perhaps for the readers it is a net positive, in that case. I do think author comments or change-notices are quite excellent at making the original point more comprehendible than the post itself. Watching the author break part of the argument and put it back together leads to understanding of the logical machinery of the argument. But admitting error, again, is not a strong Substack growth strategy.
For the author I think repetition is intellectual poison. One can latch on to every region+time snapshot that affirms the previous conclusion, crow "this is what I told you would happen," never acknowledge or tally the snapshots that contradict it. The endlessly repeated post becomes a regressively hyperlinked matryoshka of flawed "proofs" leading into blindness. This can be avoided with true rewrites, where the original evidence is reassessed.
Thanks for your well-reasoned take on this, and for a more helpful explanation of how "natural antibodies" work than Geert has ever offered.
Although I think your two possible explanations probably rank higher at this point, I would like to offer a third that may rise in relevance as more people get 3, 4, or more injections of the same genetic spike vaccines.
Specific Spike Tolerance
Foreign proteins can function as both antigens (generating an antibody and inflammatory response) and tolerogens (generating a tolerance response that inhibits inflammation). We are constantly exposed to foreign proteins that are not associated with pathogens, and when our immune system treats them as antigens the result is an allergic reaction.
Allergic reactions can often be treated by regular controlled injections of the offending protein, which activates tolerance mechanisms. I had this experience personally after developing an allergy to bee stings, which was successfully treated by allergy shots.
My concern is that the mechanism of delivery of the spike protein in genetic vaccination does not "look" to the immune system like a viral infection, and also that the ensuing antigenic response and attack on spike beating cells "looks" like an autoimmune reaction.
One expected outcome of this, which would be exacerbated by boosters, would be the activation of tolerance pathways that counteract and ultimately downregulate the initial immune response to spike protein, even as antibody levels remain high and receive a boost upon further injections.
The cells to keep an eye on here are regulatory T cells (Tregs or FoxP3+), which are well studied in cancer research (because they can prevent the immune system from recognizing and destroying metaplastic cells) but so far not much examined in the context of SARS-CoV2 vaccination.
In this case, eventually this should promote the re-evolution of SARS-2 back towards the original spike configurations (or something very similar) of the Wuhan wildtype and Alpha variants among highly vaccinated populations since the spike proteins of those variants would become even more easily tolerated as "not pathogens" than derived spike proteins of variants like Omicron (and to a lesser extent Delta).
Perhaps this could even explain why in some place Delta seems to be ongoing alongside Omicron instead of being wholly supplanted by Omicron as in South Africa.
Might this also explain the reported instances of vaccinated persons having "the worst cold ever" that "just doesn't go away"? After all if your body is going to tolerate SARS-2 due to the spike AND the residual adaptive antibodies outcompete the Natural IgM, then essentially you've placed a welcome mat for SARS-2 (or anything sufficiently similar) to come and take up INDEFINITE residency in you no?
And if "the worst cold ever" is not caused by SARS-2, then that would point more toward general immune suppression/broad tolerance, or Brian's point #1.
Well maybe, but the virus also has a whole host of other proteins that the vaccine wouldn't induce tolerance for, that will trigger a normal adaptive immune response once infection gets underway. So my thought is that it would increase the likelihood of getting past the innate immune response (i.e. more infections) without necessarily leading to chronic or more severe infection.
The main health risk I would expect in this scenario would not be a lot of Covid deaths - since Omicron appears to be legitimately milder and the immune system should preserve some capacity (e.g. with T cells and antibody memory) to fight the virus once infection gets underway. Rather it would be that each injection - and each infection that gets past the initial line of defense - leads to more spike protein exposure, which appears to have acute and potentially cumulative neurological and cardiovascular effects.
I would not expect infection to be tolerogenic, unless the virus figures out how to become dormant and exist in cells while causing minimal harm, which Brian assures me is unlikely. A virus that is actively infecting and lysing cells is going to trigger an immune response and should also lead to reduced spike tolerance. On the other hand I would expect genetic vaccination to be tolerogenic because it is not associated with other signals of viral infection.
In a very simplistic model - if tolerance is indeed occurring - I would expect each vaccination to increase spike tolerance and each infection to decrease it, with the mainstream-narrative-confounding result that the more injections one has, the more likely they are to contract the virus, and the way back to more robust immunity is through several rounds of infection with no more intervening boosters.
Would the possibility exist for continual boosters to even cause dysregulation of the immune responses that would normally be triggered by the lysing of cells?
I'm thinking about another post of Brian's titled "Liquid Cancer" and wondering if there wouldn't be some vaguely similar immune dysfunction even in the wake of things that should normally trigger a regulatory immune-mediated response (like excessive cell replication for instance).
Hmm. Autoimmune disorders are already defined by over-abundance of cellular destruction markers from self-attack. This could lead to less innate immune sensitivity to normally low-aggression invaders. Some form of rest is intuitively essential for the immune system to be able to distinguish new danger signals; the CVax boosters (and the childhood vax schedule before it) deny the immune system this rest.
I'll let Brian answer that one as I don't have a good grasp of whether and how continual boosting would mimic cell lysis.
With regard to cancer, my concern would be more along the lines that continual boosters will induce a generalized tolerance to metaplasia ("hey, our cells seem to make strange proteins sometimes, I guess that's OK") which would render NK cells and T cells less likely to catch and destroy nascent cancers.
I went back to plug in what Omicron's apparent acceleration of "negative efficacy" implies about General vs Natural Antibody Based immunosuppression (nothing, it supports both equally). But I do think it might challenge tolerance. Maybe tolerance implies that Delta should be more welcomed than Omicron...
Can you elaborate on your last two sentences? I'm not clear on whether you're saying the Omicron data is supporting or refuting the tolerance hypothesis.
If the T Cell repertoire's increased tolerance of spike is priming the vaxxed for suppressed immune response, a more recognizable spike should be more favored than a new one. Alternately, the tolerance bit could still be true but in the immediate term antibody drift - faster escape from "neutralizing" - is more relevant to innate immune suppression.
Got it. Yes it depends on the specificity of tolerance vs. antibody production. Intuitively I would expect tolerance to be broader both because tolerogens have substantial diversity in nature (e.g. pollen of related species, venom of stinging insects, etc.) and also because I would expect broad tolerance to be generally adaptive (it's not too often that something that looks molecularly like pollen shows up on a virus) while a broad antibody response will be generally maladaptive (due to increased rates of autoreactivity offsetting potential gains from anticipating future viral mutation).
This is the bit I don't understand about some folks. If in January 2019 you had asked some people if they would be willing to take 3 shots of a new vaccine that had only been out for a year or less in a span of 5 months and thereafter need another shot every 3 months...I think most would have looked at you with incredulity and been aghast. Instead, now...well, they line up for it assured that any unforeseen outcomes can be adequately handled by these same authorities and companies.
The head does swim at how many different ways the injections can miswire the immune system, especially given boosting. Possible engagement of self PRRs during spike expression certainly implies a possibility of tolerance. Stoichastic also points out the obvious potential for T Cell exhaustion in yesterday's post - https://stoichastic.substack.com/p/immunology-i-the-science - exhaustion could be seen as tolerance, or maybe just "desensitization."
And of course in Forever Spike I speculated whether the unvaccinated would be subject to the same tolerance hazard you mentioned, via constant infection pressure (or, allergic sensitization via same). For this version I tried to leave in a little negative space, so that the residual antibody point is clearer, but I might expand the footnotes to discuss the other possibilities.
In the case of the unvaccinated though would this not be less likely to occur? I'm thinking of how I've read that generally those who have been infected tend to have a longer-lasting adaptive antibody response (of course this varies from individual to individual), but this might have been the way it evolved so that tolerance situations were avoided (in some distant past, predecessor organisms with super short adaptive antibody responses suffered repeated infections frequently enough to eventually develop chronic infections of the same pathogen, thereby reducing their fitness and decreasing their ability to pass on their set of genes that resulted in the same).
If the longer lasting adaptive immune response that we see from natural infection is needed so as to avoid the negative trade off of innate immune suppression (via outcompeting it) and tolerance (by keeping infections spaced out enough that the pathogens don't get to become tolerogens (unless they really don't do anything bad to the body and reduce fitness in anyway) and this longer lasting adaptive immune response also requires the migration of resident T cells to the respiratory and GI tract, then it should follow that the unvaccinated (generally speaking of course, individual cases may differ) are unlikely to get seriously ill with one particular variant again for a number of months (is it any wonder that immunity to the 4 common cold coronaviruses apparently typically lasts 8-12 months?) though they may end up catching different variants (so catching say Beta, Lambda, Delta and Omicron in the space of a year) but these variants may be different enough so as not to promote tolerance of any one particular variant.
On the other hand the vaccinated since they are getting primed with the same spike sequence every 3 months (or less....don't be surprised if the time period drops to 45-60 days) will be training their systems to tolerate any variant matching that sequence and inviting reinfection through the innate immune suppression and lack of resident T cells in crucial areas. So they perhaps get infected often because the portcullis/gate of the outer walls is left wide open (no migrant resident T cells, no IgA) and even though initially the system clears the virus in the blood stream, especially those with the matching spike conformation (hence not stopping infection but preventing severe disease and death), eventually they get infected enough and exposed enough to that spike configuration (as well as the OTHER viral proteins) that the immune system just tolerates them. At which point the virus is free to lay siege (chronic infection) to the inner keep and potential win (severe disease, death).
In my own experience, I'm watching a few things. First, my daughter (a nurse) got Covid a year ago, presumably the first virus to circulate here. She was fairly sick for a week or so, lost her sense of taste/smell for awhile, etc. In the year since, she has been around a LOT of Covid cases in her job, and is often assigned to the "covid ward". Amusingly, in this scenario her natural immunity has been recognized and seen as valuable! She has not gotten sick again, and in fact, hasn't had a cold or anything else. Second observation: my 28 year old grandson got two Pfizer shots back in about August. Just this month he has had two colds. The first one was minor, but right now he's got a fairly bad one. He's tested weekly in his work, but is so far negative for whatever that is worth, but certainly this could indicate a less robust immune system. Two colds in a month seems odd as he has always been quite healthy and not prone to colds. Third observation is a close friend of my daughter, who had colon cancer a few years ago. She had a good recovery and was seemingly in remission. After two Pfizer shots and then a booster in September her cancer was back with a very sudden vengeance and has spread quite badly, so things don't look good for her. And then there is my 35 year old son. He was at U.C. Davis in the fall of 2019, and got quite sick with what the university health doctors called "a weird thing that is going around and we don't know what it is." It's worth pointing out that UC Davis has an enormous Chinese student population, and many from Wuhan area. He recovered with no problems and has also been fine ever since. His girlfriend at the time (she's asthmatic) got sicker than he did and at one point had to go to the E.R. where she was treated with a nebulizer and some kind of steroids, and in addition, was given Ivermectin for a short time. She also recovered, although it took several weeks to fully recover for her. So it's now 2 years since they were sick, and haven't had anything since except for minor colds that lasted a day or two. They were never tested or confirmed as Covid cases since at that time it was all a mystery, but I'm fairly sure they most likely had Covid. As for myself and my husband, we have been completely fine and refuse to possibly compromise our immune systems with this jab of whatever it is.
Right, the premise of Forever Spike* - the inspiration for the phrase - is that the disabling of innate immunity in the vaccinated leads to disruption of natural infection cycles. Because the vaccinated can't keep the virus in check, the unvaccinated experience unnaturally prolonged immune challenge from the virus, beyond the normal level of background innate suppression, risking allergic sensitization or tolerance. The seasonal ebb and flow that allowed the immune system to lower its guard so that the next immune challenge from the virus would promote renewed T Cell vigilance, or possibly an antibody update, is gone.
I've become more sanguine on the issue, given the return of some kind of seasonality in some places - though, New England and Canada are now corroborating the UK. And I still think "shedding" of spike and potential allergic/IgE sensitization is scary...
Very true (shedding of spike and allergic sensitization is truly scary), however isn't this seasonality something that happened in the context of there not been booster shots every 3-4 months? I believe in Israel they had noticed a lot of "off-season" viral infections (I think for rhinovirus and RSV) a few months back, particularly in children. This was not due to the vaccinations of course, but the speculation was that this was due children having not been exposed to the relevant viruses during what would have been the normal season and then encountering them at the time cause a large increase in infections.
Might continual boosters 3-4 times per year and the associated suppression of innate immunity when the adaptive antibody levels fall shortly thereafter each time lead to off-season outbreaks (which might still be lower and less widespread than the seasonal outbreaks) as you suddenly get a cohort of particularly susceptible individuals who are exposed to the virus (which would still be around but just not as widespread during low/off season)?
Also I meant to mention earlier that this is a brave new world we are about to enter since some of the possibilities we have been discussing may simply never have arisen with previous booster promoted vaccines like the flu shots because those boosters were only ever annual. Who knows if we might not have seen persons get their immune systems properly wrecked had the flu shot been given 4 (or more!) times per year!
How is it mechanistically possible that the jab has negative efficacy for transmission yet somehow appears to do something with respect to hospitalization and death?
Suppressed innate immunity means the "door" is left open. Pre-existing memory b-cells that ramp up anti-spike antibodies means the vault is locked up - viremia is blocked and so the virus doesn't spread to other organs. This doesn't work on the other "side" of the cells that are shedding the virus - i.e., into the airway. The tradeoff is still very much a net negative for most people since they were not at risk from severe outcomes anyway (and the data on "long covid efficacy" seems ambivalent).
*Shed into the airway or the less pleasant alternate route suggested by Ethical Skeptic
I really appreciate detailed footnotes and references.
Some random questions that I hope will be explored further:
1. What does "trained" innate immunity really mean? To me it really can only work if you are exposed to small amounts of virus/bacteria. Just enough that your immune system can handle it.
2. Sometimes I am puzzled by claims about how good children's innate immune system is.
Is it really? Aren't kids sick all the time? Come beginning of school year and until the end of
flu season, children were the biggest vector of spread of colds/flu.
3. I am still confused by "asymptomatic". And the fact that "experts" cannot definitively answer
questions, it only means that a) they don't know or b) science is not settled.
So, you are infected, but you are asymptomatic. What does that mean? Did your natural innate immunity stop the virus in time? If yes, then the adaptive immune system wasn't even engaged and therefore no specific antibodies (and further down memory cells) were generated.
Has this been cleared up? I haven't seen any compelling papers discussing this.
4. What happens if you are vaccinated and then you get infected? Do you actually develop
any long term immunity? Or vaccinal antibodies completely prevent you from developing
any sort of robust immunity (as you would if you weren't vaccinated)?
5. It seems that Omicron is the end of the line. There have been some reports that after Omicron infection there appears to be immunity against other variants as well. So, my interpretation is the following:
a. Boosters won't have any effect: either in positive sense (Omicron largely evades it) or negative (no extra evolutionary pressure since Omicron can already evade it)
b. If getting Omicron develops long-term immunity (despite being vaccinated), it means this
is the best-case scenario. By end of the spring, we'll all either get it or be exposed to it
that fairly robust herd immunity should emerge.
Where is the flaw in this logic?
6. Omicron appears mild (to me, this is the first time in the pandemic where number of
cases and hospitalizations/deaths is clearly decoupled) at the moment. What is the
evolutionary environment where another variant emerges that is as infectious *and* more virulent? From evolutionary perspective, more virulent virus would have hard time becoming dominant (it of course can emerge, but it wouldn't become dominant if equally infectious
virus is less virulent).
Again, where is the flaw in my thinking?
1. That's a doozy. On a theoretical level the question centers on whether innate immunity (Pattern Recognition -based cellular response and B-1 Cell-created Natural Antibodies) has a truly "innate" programming or whether it is, itself, a malleable pattern recognition machine (like adaptive immunity). It's seemingly a largely ignored subject, but here is a very comprehensive review of the evidence supporting the malleable model and theories how it would work: https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6986364/ Also, the research trope that the microbiome promotes overall immune function (https://pubmed.ncbi.nlm.nih.gov/15158604/ - this was an exciting frontier 10 years ago, but research seems to have dried up after 2013) would seem to argue for a need to feed the innate immune system some sort of real-life input to preserve its understanding of what given patterns *mean*, in my intuition. It must learn the language and also keep speaking it, or lose fluency. Thank you for that prompt because I forgot I had that first link. Anyway, I am still not aware of any mention of "training" Natural Antibodies as GvW alludes to.
2. Children are operating without a full repertoire of antibodies, so it make sense for them to get sick a lot as they "collect them all" (though, I rarely got sick as a child myself, perhaps thanks to being in very low-hygiene environments). But on the flip side, the fact that the common cold doesn't kill them is a demonstration of innate immune competence and there was no reason not to expect that competence to apply to a "novel" coronavirus, and indeed it proved to do so. That said, the evolutionary biology perspective might argue for a more ambivalent take - it seems implausible that the immune system was built to handle what modern human life puts it through, i.e. encounter every compatible virus in the planet as opposed to the locally popular set. So I try not to go too far with assumptions about what "normal" is for childhood immune competence. I don't know if there is actual research support for childhood transmission of flu, would be keen on seeing a paper if there's one.
3. The traditional definition of "infection" is as an explanation for resulting disease. Asymptomatic infection is just that explanation without the disease. Now that we know we're all giant space-ships full of trillions of bacteria and our own cells side by side, there's plenty of budget for viruses to replicate inside the space ship and move on without disease, with spread to the rest of the space-ship blunted by innate immunity. Where we define the boundary of "infection" becomes a bit arbitrary at that point, but the accidental boundary used for SARS-CoV-2 - PCR positive test or detectable antibodies - turned out to be a very good correlate for durable immunity (as defined by lower likelihood of meeting the boundary again)! Omicron may be blurring the correlation, it was bound to happen eventually. The earliest-known example of a virus that produces common, real-life asymptomatic infection might be polio.
4. That's the big question, as acknowledged in Footnote 14.
5a,b pretty much my thinking on the subjects. Whether boosters would even add escape pressure to Delta was always a hypothetical to begin with (maybe you could argue that they are giving Omicron an edge, but the example of South Africa already serves as a negative control against that hypothesis). As far as "herd immunity," I don't think it will ever be a meaningful term RE coronavirus or flu. The design of natural immunity is to promote their sustained cohabitation with their host (us) (see https://unglossed.substack.com/p/die-herd).
6. I confess epistemic helplessness on this question. Various folks claim various understood reasons for why the SARS-CoV-2 spike was pathogenic - such as, previous priming that creates an inflammatory / IgE response against epitopes on the spike (reinforcing the superiority of innate / non-trained immunity), or epitopes that prompt autoimmunity, or something about Strep toxin - and I would assume Omicron has dropped the relevant epitopes while preserving the core function against ACE2. But then still others say it's the temperature tropism change.
The difference between ''inoculated'' and congenital immunity is equivalent to a package vacationer posing as a native speaker in the country of the body, so to speak.
Yes, pulling out the phrase book, incapable of nuanced expression and understanding
Ah, it's sentences like these that make my days more shiny and liveable:
''No wonder modern medicine’s fixation on detectable serum antibody - induced via vaccination - has been a perpetual, Quixotic campaign targeting the wrong dragons.''
Please, please, mor of it ...
Have you seen this article? Some very scary stuff. Not sure what to make of it.
https://www.thailandmedical.news/news/omicron-might-cause-mild-symptoms-in-a-large-percentage-but-the-long-term-health-implications-are-far-worse-than-delta,-be-warned
Well, "airborne HIV" certainly wouldn't be pleasant. On the other hand it's a niche that has turned out to be occupied by other viruses, upturning the entire logic of HIV / AIDS (and apparently the new Kennedy book is persuasive that there was never a solid reason to believe that logic in the first place) - for example, Measles goes to town on immune cells https://en.wikipedia.org/wiki/Measles_morbillivirus#Infection - "airborne HIV" already exists, in other words. So the question of what it even means for any virus to exploit immune cell receptors is another giant unknown in science.
I have read so many pages of a number of immunology books and this is the first time I ever have heard of "natural antibodies". Roitt's doesn't mention them until page 302.
Thanks for the lesson.
"The ideal spectrum of epitopes for antibody targeting cannot be created; the immune system must focus exclusively on the spike and may target host-homologous epitopes that otherwise would not have been “of notice,” leading to autoimmune antibodies. The spike protein is a smorgasbord of such potential epitopes."
Oh yeah. They used pseudoiridine, which can apparently lead to stop codons failing.
https://twitter.com/JikkyKjj/status/1472805357747523586
As well as to novel frame reads / jumps, but that was already possible - normally the ORF for the spike protein, during viral infection, is being read in concert with other RNA machinery that can influence ribosomal read behavior. The 2012 paper is crazy - https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3381908/ - I never heard of anyone tricking nuclear RNP to perform a targeted nucleotide swap. Their methods are epic poem length.
Wow. This was a fantastic read. It drives home the point that for all of the advances in medicine, we essentially are throwing a monkey-wrench into a highly complex system in order to loosen one stuck gear and not giving consideration to where the wrench may end up and what damage it may inadvertently cause along the way.
I suppose now if this becomes a noticeable enough problem the solution will be to simply "upregulate" the suppressed immunity in some way via the development of a new, proprietary expensive drug that you then have to take within X days of your fifth/eighth/fourteenth/[insert number here] booster shot. Never mind what inadvertent effects this new "innate booster" drug will cause as there will be a fix for that too in time.
Thank you. Yes, everything discovered in immunology for the last 60 years has been refuting the ideas that are still the premise of vaccine development today. And yet the childhood schedule now has about one "wrench" for every one of those years of discovery.
Can't have too many wrenches I guess....
"This new study confirms, again, that these groups are night and day in their protection against infection"
is that confirmed? Or is it protection against symptoms of infection, an easily confused metric unless they are tested directly for infective particles?
Excluding PCR testing, the only meaningful distinction between infection and not infection are symptoms, immune response, and the rarer metric of viral cultures. https://www.medrxiv.org/content/10.1101/2021.08.30.21262701v1 Combines PCR positives with viral cultures and symptoms among "early" breakthrough infections and finds much less association between the latter and the other two. So even if you screened the (recently only!) Covid vaccinated, the rate of "infection" per positive test would not be as high
I could also bandy my take on the Sweden study which accidentally turned into a giant "events coincidentally happening after PCR positives" study and suggests that "false positive deaths" - deaths "with" SARS-CoV-2 - clearly show an increased trend, implying that they were lower before (due to the early period of efficacy against PCR positivity) - https://unglossed.substack.com/p/forever-spike-v11#footnote-anchor-4 - so there was "something to lose."
Given the freshly jabbed are
1. not sequestered from society
2. probably jabbed in high viral load/dose traffic locales
3. human, and unlikely to retain the "I am not vaccinated [sic] until 14 days time" info in their "jabbed = freedom" minds...
I would seriously love to see the stats of that 1-14 day post jab VE rate and the impact in general on cases, etc. It almost feels like cheating to exclude that period of time.
"Illness is a viscous cycle" was not an intentional pun.
Very interesting/helpful article, thanks!
It could well be that prior memory cells or existing Ab would prevent the needed innate response.
The survey article linked below talks about the relationship between innate and adaptive immune response to SARS-CoV-2, and notes that failure to mount an appropriate innate response prevents the development of a T-Cell response and predicts more severe or fatal illness.
"In an idealized example of a generic viral infection, the innate immune system rapidly recognizes the infection and triggers the “alarm bells” of type I IFN expression and related molecules (Weaver and Murphy, 2016) (Figure 2 A). This can occur within a couple of hours of infection. The innate immune response serves three main purposes: (1) restriction of viral replication within infected cells, (2) creation of an antiviral state in the local tissue environment, including recruitment of effector cells of the innate immune system, and (3) priming the adaptive immune response. The first two activities of the innate immune system slow down the viral replication and spread. The third is a critical requirement of the innate immune system to trigger the adaptive immune response."
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7803150/
And very interesting study, I hadn't encountered the suggestion that SARS-CoV-2 is already intrinsically suppressing innate immunity before, rather than the opposite - more inflammation predicts more severe disease, though not perfectly. I will be reading this. In https://www.science.org/doi/10.1126/sciadv.abj5629 Figure 2b high IFN still predicts severe outcomes (though there are some notable low-IFN-having Red squares in the middle group). But this could still be a "too much, too late" effect. Everything is relative when it comes to immune signaling.
Re: Footnote 1, I find repetition helps me with comprehension and retention, so I appreciate your persistence with any of your topics, especially for the complexities of immune responses. Exercise makes most things better.
But it occurs to me that just as some people comprehend quicker and retain longer, so do people have varying immune competence. Discussions like this one seem to describe how these activities are supposed to perform, but apparently some people perform better than others. Perhaps the key to solving this is determining why some people have poor outcomes while (most?) others are more successful, though still with varying difficulty. If we can figure out what makes the successful people perform better, maybe we can help the weaklings adjust themselves.
I'm currently experimenting with keto diet, using Saladino's Carnivore Code as a guide. His book is extensively researched, with about 700 citations of published research. His theories are based on LDL being a principal transport for delivering immune cells and excreting the waste from successful engagements. LDL reduction is an obsessive target for cardiologists particularly, and doctors generally, which might account for the observations of cardiac conditions being a co-morbidity. He cites studies that show improved immunity in people with higher LDL levels. Mine is high enough to cause mild panic in my doctors, but my experience during the pandemic has been so successful, I wonder if my high LDL is indeed protective, and all those statins my friends gorge on are actually increasing their risk.
Maybe it is not about ''more successful'' and ''poor'' at all, but simply about a most diverse interplay of diversities, which however all have the same ''intention'', namely to strive for an equilibrium, in order not to reach this as long as possible. Life is more than ''black'' and ''white'', more than ''0'' and ''1''. Without death worth living for life becomes a mere machine.
Or let me put it differently: Health is the slowest form of death for each individual living being, but disease is the fastest way for life itself to remain healthy. Therefore ''poor-ness'' is necessary for being ''more successful'' and each individual has its own pace and an individual range thereof.
People have different reasons for living, I suppose. Seems irrational to me to accept failure. Science is on the verge of substantially extending lifespans. People alive today will live as long as they want to. I'm going for the record.
Fascinating about the LDL. I have also been on the keto diet for several years now and I feel better on it than eating any other way. My own cholesterol readings, especially my LDL, have virtually always been what doctors deem too high, but I've firmly refused statins. On a keto diet my LDL went down a bit, but not hugely. I had a special cholesterol test done to determine LDL pattern type (fluffy or dense), and learned I have the desirable type A fluffy particle type. Fortunately, once I found that out my doctor stopped bugging me to go on statins. I'm 72, husband is 74 (and both of us have nearly identical cholesterol readings as our diets are the same). We're both slim, totally healthy, take no meds, and have not had flu or anything else for years. So I'm now intrigued by Saladino's theories on LDL. Perhaps they are correct! As for Covid, we've been around a number of people in the last 2 years who got it, but we've never gotten sick. We don't indulge in the silly testing games to check for any kind of positivity.
I went to keto after 2 years vegan, which cured most of my heart symptoms but HDL stayed low, TGL, TC, LDL high and started getting signs of afib. Saladino keto boosted HDL, chopped TGL, ekg consistently normal, but LDL and TC stayed high (though higher "fluffy" particles). Saladino says no problem, I'm continuing the experiment under watchful eye of cardiologist. Chapter 11 focuses on cardiac issues, which has 135 citations. The most directly relevant ref for immunity is an International Journal of Epidemiology article you can find at https://academic.oup.com/ije/article/26/6/1191/676876. There's a link to a pdf on that page with a very long url.
I've also experimented with diet and read Saladinos book (and listened to 100s of podcasts on the topic). Saladino now recommends not being in ketosis long term. He eats meat, fruit and honey. I experimented with that mainly for hand eczema. My skin was amazing after a month of meat and honey. Dave Feldman does interesting work on cholesterol also over at cholesterolcode.com
I have some fruit in season but I keep my carbs to about 5% and especially cautious of sugars due to alzheimers gene. We're complex organisms and all unique in many ways. I like frequent tests to keep close watch on my chemistry and consult several docs to try to keep the best balance. Thx for the link.
LDLs are obviously an essential molecule. I think throughput is what is important - they should be readily available, but also frequently called. This cannot be achieved by "reducing" LDLs, but does still imply that something is out of balance if the measurable levels are high. You may still accrue the positive, but risk the negative. My intuition is that it is the biological universality of double-edged swords like these which explain why a single day without exercise can take (arbitrary example) three days of exercise to compensate for.
Perhaps for the readers it is a net positive, in that case. I do think author comments or change-notices are quite excellent at making the original point more comprehendible than the post itself. Watching the author break part of the argument and put it back together leads to understanding of the logical machinery of the argument. But admitting error, again, is not a strong Substack growth strategy.
For the author I think repetition is intellectual poison. One can latch on to every region+time snapshot that affirms the previous conclusion, crow "this is what I told you would happen," never acknowledge or tally the snapshots that contradict it. The endlessly repeated post becomes a regressively hyperlinked matryoshka of flawed "proofs" leading into blindness. This can be avoided with true rewrites, where the original evidence is reassessed.
Thanks for your well-reasoned take on this, and for a more helpful explanation of how "natural antibodies" work than Geert has ever offered.
Although I think your two possible explanations probably rank higher at this point, I would like to offer a third that may rise in relevance as more people get 3, 4, or more injections of the same genetic spike vaccines.
Specific Spike Tolerance
Foreign proteins can function as both antigens (generating an antibody and inflammatory response) and tolerogens (generating a tolerance response that inhibits inflammation). We are constantly exposed to foreign proteins that are not associated with pathogens, and when our immune system treats them as antigens the result is an allergic reaction.
Allergic reactions can often be treated by regular controlled injections of the offending protein, which activates tolerance mechanisms. I had this experience personally after developing an allergy to bee stings, which was successfully treated by allergy shots.
My concern is that the mechanism of delivery of the spike protein in genetic vaccination does not "look" to the immune system like a viral infection, and also that the ensuing antigenic response and attack on spike beating cells "looks" like an autoimmune reaction.
One expected outcome of this, which would be exacerbated by boosters, would be the activation of tolerance pathways that counteract and ultimately downregulate the initial immune response to spike protein, even as antibody levels remain high and receive a boost upon further injections.
The cells to keep an eye on here are regulatory T cells (Tregs or FoxP3+), which are well studied in cancer research (because they can prevent the immune system from recognizing and destroying metaplastic cells) but so far not much examined in the context of SARS-CoV2 vaccination.
Robert Malone has warned of this. He calls it High Zone Tolerance.
He got me started on this line of reasoning.
In this case, eventually this should promote the re-evolution of SARS-2 back towards the original spike configurations (or something very similar) of the Wuhan wildtype and Alpha variants among highly vaccinated populations since the spike proteins of those variants would become even more easily tolerated as "not pathogens" than derived spike proteins of variants like Omicron (and to a lesser extent Delta).
Perhaps this could even explain why in some place Delta seems to be ongoing alongside Omicron instead of being wholly supplanted by Omicron as in South Africa.
Might this also explain the reported instances of vaccinated persons having "the worst cold ever" that "just doesn't go away"? After all if your body is going to tolerate SARS-2 due to the spike AND the residual adaptive antibodies outcompete the Natural IgM, then essentially you've placed a welcome mat for SARS-2 (or anything sufficiently similar) to come and take up INDEFINITE residency in you no?
And if "the worst cold ever" is not caused by SARS-2, then that would point more toward general immune suppression/broad tolerance, or Brian's point #1.
Well maybe, but the virus also has a whole host of other proteins that the vaccine wouldn't induce tolerance for, that will trigger a normal adaptive immune response once infection gets underway. So my thought is that it would increase the likelihood of getting past the innate immune response (i.e. more infections) without necessarily leading to chronic or more severe infection.
Fair enough. So more frequent reinfections but not necessarily chronic infections.
Though, would not the aspect of frequent enough reinfections then eventually promote tolerance towards the other viral proteins?
The main health risk I would expect in this scenario would not be a lot of Covid deaths - since Omicron appears to be legitimately milder and the immune system should preserve some capacity (e.g. with T cells and antibody memory) to fight the virus once infection gets underway. Rather it would be that each injection - and each infection that gets past the initial line of defense - leads to more spike protein exposure, which appears to have acute and potentially cumulative neurological and cardiovascular effects.
I would not expect infection to be tolerogenic, unless the virus figures out how to become dormant and exist in cells while causing minimal harm, which Brian assures me is unlikely. A virus that is actively infecting and lysing cells is going to trigger an immune response and should also lead to reduced spike tolerance. On the other hand I would expect genetic vaccination to be tolerogenic because it is not associated with other signals of viral infection.
In a very simplistic model - if tolerance is indeed occurring - I would expect each vaccination to increase spike tolerance and each infection to decrease it, with the mainstream-narrative-confounding result that the more injections one has, the more likely they are to contract the virus, and the way back to more robust immunity is through several rounds of infection with no more intervening boosters.
Would the possibility exist for continual boosters to even cause dysregulation of the immune responses that would normally be triggered by the lysing of cells?
I'm thinking about another post of Brian's titled "Liquid Cancer" and wondering if there wouldn't be some vaguely similar immune dysfunction even in the wake of things that should normally trigger a regulatory immune-mediated response (like excessive cell replication for instance).
Hmm. Autoimmune disorders are already defined by over-abundance of cellular destruction markers from self-attack. This could lead to less innate immune sensitivity to normally low-aggression invaders. Some form of rest is intuitively essential for the immune system to be able to distinguish new danger signals; the CVax boosters (and the childhood vax schedule before it) deny the immune system this rest.
I'll let Brian answer that one as I don't have a good grasp of whether and how continual boosting would mimic cell lysis.
With regard to cancer, my concern would be more along the lines that continual boosters will induce a generalized tolerance to metaplasia ("hey, our cells seem to make strange proteins sometimes, I guess that's OK") which would render NK cells and T cells less likely to catch and destroy nascent cancers.
I went back to plug in what Omicron's apparent acceleration of "negative efficacy" implies about General vs Natural Antibody Based immunosuppression (nothing, it supports both equally). But I do think it might challenge tolerance. Maybe tolerance implies that Delta should be more welcomed than Omicron...
Can you elaborate on your last two sentences? I'm not clear on whether you're saying the Omicron data is supporting or refuting the tolerance hypothesis.
If the T Cell repertoire's increased tolerance of spike is priming the vaxxed for suppressed immune response, a more recognizable spike should be more favored than a new one. Alternately, the tolerance bit could still be true but in the immediate term antibody drift - faster escape from "neutralizing" - is more relevant to innate immune suppression.
Got it. Yes it depends on the specificity of tolerance vs. antibody production. Intuitively I would expect tolerance to be broader both because tolerogens have substantial diversity in nature (e.g. pollen of related species, venom of stinging insects, etc.) and also because I would expect broad tolerance to be generally adaptive (it's not too often that something that looks molecularly like pollen shows up on a virus) while a broad antibody response will be generally maladaptive (due to increased rates of autoreactivity offsetting potential gains from anticipating future viral mutation).
One thing for sure is the human race is doing their best to prove you right. Triple-dosing after only 3 months now recommended in France! 3!
We are going with 4 months in Australia. So tragicomical to see the exhortations for booster asap while I sit here unjabbed.
This is the bit I don't understand about some folks. If in January 2019 you had asked some people if they would be willing to take 3 shots of a new vaccine that had only been out for a year or less in a span of 5 months and thereafter need another shot every 3 months...I think most would have looked at you with incredulity and been aghast. Instead, now...well, they line up for it assured that any unforeseen outcomes can be adequately handled by these same authorities and companies.
The head does swim at how many different ways the injections can miswire the immune system, especially given boosting. Possible engagement of self PRRs during spike expression certainly implies a possibility of tolerance. Stoichastic also points out the obvious potential for T Cell exhaustion in yesterday's post - https://stoichastic.substack.com/p/immunology-i-the-science - exhaustion could be seen as tolerance, or maybe just "desensitization."
And of course in Forever Spike I speculated whether the unvaccinated would be subject to the same tolerance hazard you mentioned, via constant infection pressure (or, allergic sensitization via same). For this version I tried to leave in a little negative space, so that the residual antibody point is clearer, but I might expand the footnotes to discuss the other possibilities.
In the case of the unvaccinated though would this not be less likely to occur? I'm thinking of how I've read that generally those who have been infected tend to have a longer-lasting adaptive antibody response (of course this varies from individual to individual), but this might have been the way it evolved so that tolerance situations were avoided (in some distant past, predecessor organisms with super short adaptive antibody responses suffered repeated infections frequently enough to eventually develop chronic infections of the same pathogen, thereby reducing their fitness and decreasing their ability to pass on their set of genes that resulted in the same).
If the longer lasting adaptive immune response that we see from natural infection is needed so as to avoid the negative trade off of innate immune suppression (via outcompeting it) and tolerance (by keeping infections spaced out enough that the pathogens don't get to become tolerogens (unless they really don't do anything bad to the body and reduce fitness in anyway) and this longer lasting adaptive immune response also requires the migration of resident T cells to the respiratory and GI tract, then it should follow that the unvaccinated (generally speaking of course, individual cases may differ) are unlikely to get seriously ill with one particular variant again for a number of months (is it any wonder that immunity to the 4 common cold coronaviruses apparently typically lasts 8-12 months?) though they may end up catching different variants (so catching say Beta, Lambda, Delta and Omicron in the space of a year) but these variants may be different enough so as not to promote tolerance of any one particular variant.
On the other hand the vaccinated since they are getting primed with the same spike sequence every 3 months (or less....don't be surprised if the time period drops to 45-60 days) will be training their systems to tolerate any variant matching that sequence and inviting reinfection through the innate immune suppression and lack of resident T cells in crucial areas. So they perhaps get infected often because the portcullis/gate of the outer walls is left wide open (no migrant resident T cells, no IgA) and even though initially the system clears the virus in the blood stream, especially those with the matching spike conformation (hence not stopping infection but preventing severe disease and death), eventually they get infected enough and exposed enough to that spike configuration (as well as the OTHER viral proteins) that the immune system just tolerates them. At which point the virus is free to lay siege (chronic infection) to the inner keep and potential win (severe disease, death).
In my own experience, I'm watching a few things. First, my daughter (a nurse) got Covid a year ago, presumably the first virus to circulate here. She was fairly sick for a week or so, lost her sense of taste/smell for awhile, etc. In the year since, she has been around a LOT of Covid cases in her job, and is often assigned to the "covid ward". Amusingly, in this scenario her natural immunity has been recognized and seen as valuable! She has not gotten sick again, and in fact, hasn't had a cold or anything else. Second observation: my 28 year old grandson got two Pfizer shots back in about August. Just this month he has had two colds. The first one was minor, but right now he's got a fairly bad one. He's tested weekly in his work, but is so far negative for whatever that is worth, but certainly this could indicate a less robust immune system. Two colds in a month seems odd as he has always been quite healthy and not prone to colds. Third observation is a close friend of my daughter, who had colon cancer a few years ago. She had a good recovery and was seemingly in remission. After two Pfizer shots and then a booster in September her cancer was back with a very sudden vengeance and has spread quite badly, so things don't look good for her. And then there is my 35 year old son. He was at U.C. Davis in the fall of 2019, and got quite sick with what the university health doctors called "a weird thing that is going around and we don't know what it is." It's worth pointing out that UC Davis has an enormous Chinese student population, and many from Wuhan area. He recovered with no problems and has also been fine ever since. His girlfriend at the time (she's asthmatic) got sicker than he did and at one point had to go to the E.R. where she was treated with a nebulizer and some kind of steroids, and in addition, was given Ivermectin for a short time. She also recovered, although it took several weeks to fully recover for her. So it's now 2 years since they were sick, and haven't had anything since except for minor colds that lasted a day or two. They were never tested or confirmed as Covid cases since at that time it was all a mystery, but I'm fairly sure they most likely had Covid. As for myself and my husband, we have been completely fine and refuse to possibly compromise our immune systems with this jab of whatever it is.
Right, the premise of Forever Spike* - the inspiration for the phrase - is that the disabling of innate immunity in the vaccinated leads to disruption of natural infection cycles. Because the vaccinated can't keep the virus in check, the unvaccinated experience unnaturally prolonged immune challenge from the virus, beyond the normal level of background innate suppression, risking allergic sensitization or tolerance. The seasonal ebb and flow that allowed the immune system to lower its guard so that the next immune challenge from the virus would promote renewed T Cell vigilance, or possibly an antibody update, is gone.
*https://unglossed.substack.com/p/forever-spike#footnote-anchor-13 to skip the part already repackaged in today's essay.
I see (I recall the premise now that you brought it back up). So everybody gets fucked.
I've become more sanguine on the issue, given the return of some kind of seasonality in some places - though, New England and Canada are now corroborating the UK. And I still think "shedding" of spike and potential allergic/IgE sensitization is scary...
Very true (shedding of spike and allergic sensitization is truly scary), however isn't this seasonality something that happened in the context of there not been booster shots every 3-4 months? I believe in Israel they had noticed a lot of "off-season" viral infections (I think for rhinovirus and RSV) a few months back, particularly in children. This was not due to the vaccinations of course, but the speculation was that this was due children having not been exposed to the relevant viruses during what would have been the normal season and then encountering them at the time cause a large increase in infections.
Might continual boosters 3-4 times per year and the associated suppression of innate immunity when the adaptive antibody levels fall shortly thereafter each time lead to off-season outbreaks (which might still be lower and less widespread than the seasonal outbreaks) as you suddenly get a cohort of particularly susceptible individuals who are exposed to the virus (which would still be around but just not as widespread during low/off season)?
Also I meant to mention earlier that this is a brave new world we are about to enter since some of the possibilities we have been discussing may simply never have arisen with previous booster promoted vaccines like the flu shots because those boosters were only ever annual. Who knows if we might not have seen persons get their immune systems properly wrecked had the flu shot been given 4 (or more!) times per year!