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Second and last reply to M. Yeadon

Michael Yeadon’s rhetoric that mass vaccination campaigns do not have the potential to promote circulation of more infectious immune escape variants and that more infectious variants are not problematic are not based on sound immunological grounds at all. This will be my second but last reply to his erroneous and misleading interpretations. I hate to do this since this may leave the public with the opinion that people like me have nothing else to do than to focus on their own ego, although nothing is less true. However, when the most compelling arguments for my warning about the potentially disastrous consequences of mass vaccination are wiped from the table with scientifically hollow and invalid arguments, one has no choice but to react. Now, more than ever before, criticism is indispensable to build and consolidate a consensus on why mass vaccination campaigns (using the current vaccines in the heat of a pandemic caused by a highly mutable virus) are highly problematic. However, it doesn’t help when people bring to the table arguments that are scientifically incorrect.


Yeadon is basically not understanding the difference between viral escape from protection-blocking immunity and viral escape from infection-/ transmission-blocking immunity.


His rhetoric about conserved T cell epitopes and long-lived cross-reactive MHC cl I-restricted responses to those, relate to protection against clinical disease but not against infection! Yeadon doesn’t seem to understand the mechanism of S-directed immune selection, let alone adaptation of variants to conditions of suboptimal, S-directed immune pressure, which become increasingly prevalent upon mass vaccination. I can barely believe that someone who claims to be a skilled expert in immunology doesn’t see the parallel to serial in vitro cell culture passage of a mutable virus in the presence of suboptimal antibody (Ab) concentrations. In case of CoV inoculated on permissive cells, one would incubate the inoculated cell culture in the presence of suboptimal S-specific Abs to place infectious pressure on viral infectiousness. Provided you harvest the viral progeny and use it to repeat this procedure a number of times, you’ll manage to progressively enrich the viral progeny with naturally occurring S variants that have been selected to overcome the immune pressure placed on the S protein and which are, therefore, more infectious in nature. As the selected immune escape variants are so to speak ‘trained’ to reproduce more efficiently, they will now enjoy a competitive advantage in comparison to the wild strain. This is to say that they will now become the dominant variant/ strain! All this occurs of course in the absence of T cells or any kind of active immune response. One simply uses a biological (i.e. an Ab), instead of a chemical or physical agent, to select adequate mutants and enable them to adapt. I don’t get it that Yeadon doesn’t understand that this is highly similar to Sars-CoV-2 being ‘inoculated’ on epithelial cells from humans experiencing suboptimal S-directed immune pressure only (!), as is the case in (a large number of!) people who are in the process of mounting Abs in response to S-based vaccines or who are sitting on short-lived, suboptimal S-specific Abs following asymptomatic infection. In none of these cases the S-directed Abs are accompanied by cytolytic MHC cl I-restricted T cells! Again, when it comes to fighting more infectious variants, Yeadon argues that because of their high degree of sequence homology, variants are ‘irrelevant from an immunological standpoint’. Again, he doesn’t seem to capture that even a single mutation can make a big difference when it enables enhanced infectiousness and is comprised within a variant that is repeatedly exposed to conditions that precisely exert immune pressure on viral infectiousness. Again, in terms of clinical protection and recovery from disease, CTLs can deal with all of them and I never pretended the opposite. However, more infectious variants will make rise the infection rate in the population, thereby increasing the likelihood that previously asymptomatically infected people get re-infected by a variant within a few weeks (1-6w) after their primary infection. This is at risk of enhancing their susceptibility to the disease as their natural Abs may be sufficiently suppressed by their suboptimal S-specific Abs to no longer be able to eliminate the virus via innate immune cells (most likely NK cells). Yeadon may want to educate himself on natural/ innate Abs and their relevance in fighting a multitude of different pathogens, not just viruses and not only CoV but, for example, also Influenza virus.


The bottom-line is that Yeadon is far more eloquent than I am and that I would certainly prefer if he would lead the discussion when it comes to opposing the madness of mass vaccination campaigns. However, as long as he’s mistaken about the high likelihood for these campaigns to drive the adaptation of more infectious variants and the issue that comes with those, I cannot concur with his strategy for countering the mass vaccination program.


In the text below, I have only added comments when Yeadon’s arguments have not already been sufficiently countered by all of the above.


"As usual, GVB skirts the entire issue of T-cells and their breadth of antigenic virus recognition and appears to want to base his fear mongering solely on the role of antibodies. As for the mechanism of host protection I describe - which is absolutely classical & not considered theoretical at all - how else does GVB propose host immunity works? If you’ve acquired immunity from surviving infection or having been vaccinated, but then don’t see the virus again for months, most likely you won’t have appreciable quantities of circulating antibodies. But you will have circulating T-cells capable of recognising up to several dozen virus short peptides which he’s right to point out are presented in conjunction with appropriate MHC. It’s therefore also true that some of your cells do need to become infected before your immune system recognises that the virus is present. And this is fine, because immunity doesn’t necessarily prevent SUBCLINICAL infection but it does protect you against CLINICAL illness. No variant so far differs sufficiently from the original virus to have ANY chance of escaping immunity conferred in the way which has been demonstrated in several peer reviewed journal articles over the last year. If this wasn’t true, by now we’d be seeing reinfection accompanied by CLINICAL illness all over the world. And we’re not seeing that, anywhere. Do please remember, PCR tests don’t distinguish reliably clinical illness from sub clinical infection (or downright errors in the test). So when I see news articles claiming reinfection, notice they always & only speak of the distorted language of ‘cases’, entirely the wrong term for a symptomless person with a positive PCR at high cycle threshold. SARS-CoV-2 creates a great many variants but it’s easiest to distinguish the effect of these on resilience of host protection by reference to how DIFFERENT these variants are from the original virus. If you were to create an image of the original virus & then superimpose all the variants, one after another, it would seem as if the virus remains where it is, vibrating, as it were. Much activity, but little change in its overall structure.

In every case to date, the changes are irrelevantly tiny, a handful of amino acids out of almost 10,000. This means the majority of those MHC-restricted peptides are unchanged from variant to variant. Our immune systems have absolutely no difficulty whatsoever in recognising these as a virus we’ve encountered before & this means we rapidly recruit T-cell clones, selected-for during the acquisition of immune memory, and it is these rapidly available T-cells which protect us from clinical illness by killing those small numbers of virus-infected cells. This all happens without us even becoming aware of our wonderful protective immune system.

We will not remain sub clinically infected for long enough to grow a sufficiently large virus load to become infectious."


First, the last part of the sentence above should probably read as ‘….more infectious’. Further comments below next §.


So this notional selection pressure won’t get much of a chance to operate. In fact, think about it: when was the longest time during which the virus was able to replicate unhindered? That’s right: during the initial infection. That allowed several days to a couple of weeks before an immunocompetent host mounts a sufficient response to overwhelm the virus. And it’s during that process that a selection pressure could operate, yet it’s out of this activity that the variants arose.


Is Yeadon now saying that viral variants arose as a result from immune selection pressure exerted on the virus during the early stage of infection? First, immune pressure exerted by a nascent immune response does not allow immune escape variants to become dominant as this requires adaptation. Adaptation results from repetitive breeding of a selected immune escape variant under conditions enabling it to reproduce and propagate more efficiently. So, emerging immune escape variants that are shed would need to infect other subjects who are experiencing early stage viral infection as well to ensure that suboptimal (i.e., nascent) immune conditions are reproduced. This is basically not possible as viral re-infection during the early stage of primary infection is inhibited by a number of nonantigen-specific innate mechanisms including interferons. So, variants do not arise as a consequence of a mounting immune response to natural infection!


Yet still, almost everyone clears the infection. So much for “variants formed under selection pressure are likely to be more dangerous & escape immunity”. Clearly, this is precisely NOT occurring. The only variants forming are those so close-in to the original virus that they’re not escaping immunity at all.


To state again: ‘more infectious’ variants escape immune pressure on S by selecting mutations that increasingly converge to S domains facilitating binding to the ACE-2 receptor on permissive cells.


To state again: the number of variants of SARS-CoV-2 formed is theoretically very large but, so long as they are all nearly identical to the original - which ALL of them are - they’re irrelevant from an immunological standpoint. (I recognise that some might have different behaviours as infectious agents, but that’s a separate topic entirely)."


I’ve addressed this short-sighted view above. The issue is not individual protection against disease but enhanced circulation of more infectious variants that are indirectly threatening the first line of variant-nonspecific immune defense in previously asymptomatically infected people, thereby increasing their susceptibility to disease!


I’d be interested in GVB’s response to my characterisation so far, because I genuinely don’t understand his narrative at all & I have tried, having listened to two of his long form interviews.


I’m advising Yeadon to listen more attentively…


Is he saying that the variants of SARS-CoV-2 are much more different from the original sequence than I’m relating? If yes, please provide a link to this. I’m not seeing any such larger changes in the literature. Or, is he saying that a change as tiny as I’m talking about (0.3% or so in the primary sequence) is enough to no longer be recognised as a pathogen we’ve seen before? If so, perhaps he’d like to comment on how that could be & in particular, I’d be very interested in his thoughts on these two papers? https://biorxiv.org/content/10.1101/2020.05.26.115832v1… This paper by Le Bert et al (2020) shows that those who recovered from infection with SARS in 2003 still retain good T-cell immune recognition 17y later AND also recognise SARS-CoV-2, which they’d NOT encountered before, Now, that’s cross protection & these two viruses differ by more than 20%. Rather destroys any argument that the tiny extent of drift of SARS-CoV-2 requires the planetary obsession of which GVB is part, does it not?https://sciencedirect.com/science/article/pii/S266637912100015X… This paper by Tarke et al (2021) shows that a large number of T-cell epitopes are selected & form part of the repertoire in immunity (there’s another set of smaller, overlapping but non-identical set of epitopes against which antibodies are raised). The authors themselves conclude that their findings remove concern that small changes in the virus, ...such as we’ve seen so far, will enable immune escape.https://biorxiv.org/content/10.1101/2021.02.27.433180v1… The same group also showed that subjects who’d survived infection by SARS-COV-2 or had been vaccinated ALL recognised ALL the variants which the investigators had available.


To state again: None of this is relevant when it comes to assessing virus escape from immune responses pressurizing viral infectiousness. Such immune responses exclusively involve S-specific Ab responses, not the T cell epitopes MY continues peddling with.


By the way, I’d be be interested in his reactions to this in depth review on the clinical efficacy of ivermectin. Its been subject to ruthless censorship for at least SIX MONTHS, resulting in countless avoidable deaths. I argue that if it, along with the other useful treatments, (which have been beautifully summarised in a protocol for targeted, sequential, multi drug treatment of covid19, which Dr Peter McCullough & others have drafted & posted on the website of the American Association of Physicians & Surgeons), were more widely appreciated & APPLIED in clinical practise, we could control covid19 much better than we do now, and CANCEL the Emergency Use Authorisations for all the experimental, gene-based, spike protein inducing ‘vaccines’. Does GVB agree, or is he interested only in peddling further, also experimental vaccines?


Of course, I am very supportive of the use of ivermectine. It’s just that I don’t think that it will allow eradication of this virus (which is – what I think – we need to do). Of course…unless it would be broadly used for prophylaxis. I am not sure this is really feasible and doing so might promote resistance to this drug…


Ivermectin review: https://ncbi.nlm.nih.gov/pmc/articles/PMC8088823/pdf/ajt-28-e299.pdf… McCullough et al multi drug treatment of covid19: https://medrxiv.org/content/10.1101/2021.01.28.21250706v1.full… And also: https://pubmed.ncbi.nlm.nih.gov/33387997

Bottom line for me is that the extent of variation in SARS-COV-2 simply isn’t concerning. There’s no hint of immune escape nor would it be expected, based on both theoretically & empirically.


Yeadon needs to weigh his words as he is not understanding the difference between protection against infection as compared to protection against clinical disease. Coming back with the argument that almost no vaccine, and certainly not the ‘recombinant’ ones, protects against infection will not help. While this is correct, it has been my argument all over that this is precisely the reason why we should not be using this type of vaccines for mass vaccination campaigns conducted in the heat of a pandemic of a highly mutable virus.


If the picture changes, so too will my view. This means THERES NO JUSTIFICATION WHATSOEVER FOR VACCINES AGAINST VARIANTS!!


These are definitely not my words. I have never been advocating for a third shot as it will primarily recall previously primed Abs (due to antigenic sin).


Anyone know what’s in those “3rd jab vials”? I’m often asked “So why do we require new vaccines against influenza each year?” This is because the way flu changes it’s structure is COMPLETELY DIFFERENT from the slow, antigenic drift we observe in SARS-COV-2. Instead, flu can undergo reassortment or antigenic SHIFT, exchanging whole sections of genetic information. In terms of the movement analogy, for flu, it’s as if it has its ‘seven league boots on’. It can combine these methods & in a year, evolve so much that, when it cones round again in the next season, it can actually present to our immune systems as if it was a new pathogen entirely. It doesn’t always do this and has been reasonably stable in recent years. bioRxiv


Even small changes (in HA and NA) may no longer be recognized by the host immune system and cause sickness (especially if small changes accumulate over time or if a small change occurs in a particularly important location on the HA). In other words, antigenic drift may already suffice to make a person susceptible to flu infection again. Antigenic drift is the main reason why people can get the flu more than one time (and why the flu vaccine composition must be reviewed each year). Yeadon may wonder why this occurs. Could it be that waning pre-existing vaccinal Abs allow HA/ SA-directed immune escape variants to be selected and adapt? As some people never got the disease (and hence, have no antigen-specific memory CTLs), they may need to rely on their yearly Flu shot. A nice example , indeed, of the difference between ensuring protection by preventing infection versus by preventing disease.…..

(https://biorxiv.org/content/10.1101/2020.05.26.115832v1…)". Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals.

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