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Do You No Wrong Again Khmer

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Specific narratives of antivaccine misinformation most whatever given vaccine generally consist of a combination of a subset (or all) of the following elements. First, of class, the narrative must, as all antivaccine narratives practise, include a conspiracy theory, such equally efforts by "them" (e.g., the authorities, large pharma) are trying to keep "The Truth" virtually vaccines from the public. Second, that "truth" nigh the vaccine, co-ordinate to antivaccine narratives, is that information technology is dangerous—and preferably ineffective every bit well. Examples are numerous, and regular readers of this blog are familiar with the harms that antivaxxers falsely aspect to vaccines; e.thou., autism, autoimmune diseases, cancer, and even death. To support the narrative of harm from vaccines, antivaxxers routinely portray vaccines as laden with toxins and made with "aborted fetal tissue" and "fetal cells". It'due south not enough, though, for antivaxxers to portray vaccines as dangerous to but the people receiving them. They have to portray vaccines equally dangerous to others who accept not received them as well. Before COVID-nineteen, antivaxxers tried to claim that the recently vaccinated were dangerous because they "shed" virus from the vaccine (this does happen but is not dangerous and cases of disease from vaccine shedding are exceedingly rare). Unsurprisingly, in a instance of everything old existence new again, antivaxxers have co-opted many of tried-and-not-truthful narratives and deployed them in the service of spreading fearfulness about COVID-19 vaccines, including the merits that they are made with "fetal cells", portraying the lipid nanoparticles in them every bit horrifically toxic, and the mRNA in the Pfizer and Moderna vaccines every bit "experimental gene therapy" that "hacks the software of life". They've even falsely claimed that COVID-xix vaccines cause cancer, Alzheimer'south illness, and expiry. But what about shedding?

When COVID-xix vaccines based on mRNA technology were start introduced, I naively idea that antivaxxers would non exist able to arrange the narrative of the vaccinated being a danger to the unvaccinated due to "shedding", considering the mRNA engineering used by Moderna and Pfizer/BioNTech induces cells in the recipient merely to make a single poly peptide from SARS-CoV-2, the coronavirus that causes COVID-xix. Similarly, COVID-nineteen vaccines based on adenovirus vectors, such as the AstraZeneca and Johnson & Johnson manufacture, simply use a different method to achieve the aforementioned goal: To produce the SARS-CoV-2 fasten protein and thereby produce an immune response. None of the electric current COVID-19 vaccines produces a full intact coronavirus, non even a weakened ane, as live-adulterate virus vaccines, such as the measles vaccine, utilise a weakened version of the measles virus. To summarize, current COVID-nineteen vaccines neither comprise coronavirus, killed or live-attenuated, nor can they produce a total virus. None of this science stopped antivaxxers from adopting their narrative of "shedding" from vaccines as being a danger to those around the vaccinated. They happily started portraying the spike protein as deadly and falsely claimed that the vaccinated were "shedding" spike protein, leading to disease, menstrual disturbances, and fifty-fifty miscarriages in those exposed.

Over the final month, in that location have been three new papers that accept been making the rounds among antivaxxers as "scientific proof" that non only is the coronavirus fasten protein highly toxic to the vaccinated but that it is produced past the vaccinated in amounts that can cause those toxic effects. I thought I'd take some time to take a look at them. The outset ii papers are often presented as "slam dunk" evidence that the coronavirus spike protein is toxic and deadly (and, therefore, the COVID-19 vaccines are mortiferous), while the concluding paper is presented as evidence that mRNA vaccines produce enough spike protein to poison recipients. Spoiler alert: None of these papers testify what antivaxxers correspond them every bit showing, peculiarly the tertiary ane.

Fasten proteins and pulmonary hypertension

The starting time of these papers was i that I first noticed nearly a month ago on Twitter, although the study was older than that, dating back to January:

And here'due south the study, from Georgetown and the Ukraine, "SARS-CoV-ii Spike Poly peptide Elicits Jail cell Signaling in Homo Host Cells: Implications for Possible Consequences of COVID-xix Vaccines".

Information technology turns out that this "study" isn't even a written report at all. Rather, it'south more like a "news and views" or opinion piece, a review article if you're feeling particularly generous. Moreover, it was published in Vaccines (Basel), an open access periodical in the MDPI group of journals. Unsurprisingly, MDPI journals are pretty dubious, with MDPI having been listed on Beale's listing of predatory journals in 2013. It ultimately successfully appealed and was removed from the listing. Yet, from my perspective, I do not consider MDPI journals as existence high quality and would never publish in one.

But what about the newspaper itself? Let'southward simply say that I was quite…underwhelmed…by it. Indeed, rarely in my many years of reading scientific papers accept I seen so few experiments cited in a review article do such heavy lifting to provide such weak evidence for a decision like the claim that the fasten poly peptide can cause pulmonary hypertension.

At its essence, pulmonary hypertension is high blood pressure in the lungs. The circulatory organization is divided into two components, the pulmonary system, in which blood flows through the blood vessels in the lungs, picks up oxygen, and then flows to the systemic apportionment (the residual of the trunk) to deliver that oxygen to the tissues. The pulmonary vascular system is a much lower pressure level arrangement than the systemic circulation, which is why the right ventricle, the chamber of the heart that pumps blood through the lungs, is less muscular than the left ventricle, which pumps claret through the rest of the body. In whatever event, pulmonary hypertension tin can be caused by a number of things, including some types of congenital heart disease, connective tissue disease, coronary artery disease, high blood pressure, liver affliction (cirrhosis), claret clots to the lungs, and chronic lung diseases like emphysema. The sequelae of pulmonary hypertension can be severe, including right-sided heart failure, hemorrhage in the lung, clotting, pulmonary artery dissection, and more. Let'south just say that pulmonary hypertension can be very bad.

On what do these authors base of operations their merits that spike poly peptide can cause pulmonary hypertension? They cite the most tenuous of prove, and not very much of it. For instance, The first study is nothing more than a jail cell culture study coupled with a postmortem study of lungs first published last August, in which the authors (who happened to exist them—yes, they cited their own paper) combined observations to make the leap to speculation that spike protein lone can cause the problems seen in COVID-19. In the prison cell civilization component, the authors treated the cells that line pulmonary arteries (pulmonary artery endothelial cells) and the shine muscle that surrounds the endothelial cells with spike protein and institute that spike protein can crusade intracellular signaling in these cells of a sort associated with cell injury. They likewise examined postmortem lung tissues from patients who died of COVID-19 and found pulmonary vascular wall thickening, a hallmark of pulmonary arterial hypertension. That'southward it. No, actually, that'south it. To be fair, the authors did compare the lungs of patients who died of H1N1 influenza to those who died of COVID-19 and establish that the pulmonary arteries were markedly thicker in the patients who died of COVID-xix. It's an interesting ascertainment, just if there'south one affair that was observed early in the pandemic it's that the ARDS (acute respiratory distress syndrome) caused by COVID-19 was like nothing critical intendance doctors had ever seen before.

In that location is no more, at least not from these authors. Certain, they do cite two other papers, one from 2005 showing that injecting mice with recombinant spike protein from SARS reduced the ACE2 expression and worsened acid-induced lung injury. The other paper is from December and reports that the full-length SARS-CoV-ii spike protein activated NF-κB (a signaling pathway I'm well familiar with) and AP-i transcription factors as well equally p38 and ERK mitogen-activated protein kinases. Again, you lot don't need to know the details other than that these are survival and growth pathways, but also that this observation was not made in cells from the pulmonary vasculature, but rather from a prison cell line (A549) from the lungs and some other (Huh7.5) from the liver. The relevance of this study to whether fasten protein can crusade pulmonary hypertension is questionable at best.

At present that's information technology: One study past the authors, two observations, 1 involving spike poly peptide and one involving actual viral infection, plus an old study of SARS spike protein. I say this considering it needs to be emphasized that what the authors reported was in patients who died of infection with the whole virus, SARS-CoV-2. You lot have to dissever the furnishings of full infection and the effect of fasten protein lonely, and the authors did non do this, other than equally a prelude to speculation that spike protein lone might cause pulmonary hypertension. Even for "proof" commonly cited by antivaxxers, this was weak sauce.

The deadly spike protein, have two

Near three weeks agone, antivaxxers started pointing to a study from the Salk Institute as yet more "proof" that the spike protein used in COVID-nineteen vaccines is toxic and deadly. For instance, behold Alex Berenson, the "pandemic's wrongest man", exultation near the report:

I was tickled when I saw these Tweets to meet Berenson utilise a term like "off-target effects" as if he actually knows what it means.

Information technology turns out that this study on a preprint server has been published in Apportionment Research. Information technology also turns out—surprise! surprise!—to definitely not to be "smoking gun" bear witness for Berenson'southward claims. Unlike the case of many papers cherry picked by antivaxxers to support their claims, it's non that the paper is horrible, either. It's not. Information technology's pretty decent, really, at least as a preliminary, primarily observational study. Fifty-fifty more amusing, in information technology the authors expressly draw how their work actually demonstrates why vaccines that apply spike protein every bit the antigen are so effective, and the Salk Institute press release even includes a disclaimer that the spike proteins made in cells past SARS-CoV-2 "behave very differently than those safely encoded by vaccines".

Allow'south look at the paper itself. The kickoff thing that those of y'all with access to the paper volition notice is how short it is: Iii pages, ane figure. That'south because it's not a full research newspaper, only rather a inquiry letter. As a outcome, there'southward no detailed Methods section, and the results are very briefly described (much likewise briefly, for my liking). To be honest, for some of the experiments, due to the brevity of the newspaper, I had a bit of a hard fourth dimension making heads or tails of what, exactly, the investigators did. I'll practise my all-time trying to explain, however.

In brief, the researchers used a "pseudovirus" that was surrounded by a "crown" of fasten protein, like the coronavirus, but did non contain actual virus, dubbed Pseu-Spike past the authors. What is a pseudovirus? A reasonable question. In brief, a pseudovirus is a construct that has the external proteins of the virus of involvement. There are a multifariousness of pseudoviruses now, every bit described in this commodity in The Scientist:

Among these, researchers turned to models of the pathogen such as pseudoviruses and chimeric viruses that can be studied safely in labs with lower biosafety level (BSL) clearance than required for studying the wildtype version, in an attempt to aggrandize the report of the novel coronavirus. Pseudoviruses don't replicate, rendering them harmless, just by replacing their surface envelope proteins with those of SARS-CoV-two, researchers can glean insights into the ways the pathogen infects cells.

And:

Pseudoviruses were first developed in the 1960s, after scientists began studying a vesicular stomatitis virus (VSV) isolated from cattle. In improver to replicating well in culture, they afterwards learned that its surface protein, VSV-G, facilitates entry into all eukaryotic cells, making the virus a useful vector not only as a pseudovirus just as a ferry to evangelize DNA into cells for therapeutic purposes. The first Ebola vaccine was adult using a VSV platform, and more than recently, the virus has been engineered to seek out and destroy cancer cells.

HIV-based platforms, which came about in the 1980s, have since replaced VSV as the most mutual model for developing both pseudo- and chimeric viruses. Unlike VSV's negative-strand RNA genome that must be transcribed in one case within the cell, HIV'due south positive-strand RNA genome can instantly begin translation, making pseudoviruses based on HIV faster to produce. HIV-based model viruses have now been used in many of the same applications equally VSV, with scientists applying them to the study of diseases such equally AIDS, SARS, MERS, and influenza.

Likewise, compared with natural virus, a pseudovirus can just infect cells in a unmarried round, has broad host range, high titer, and is non easily inactivated past serum complement.

Unfortunately, it is not clear from the paper which of these platforms was used to produce the pseudovirus in the experiments or how that pseudovirus was adult and produced. This is the sort of information that a total-length inquiry newspaper would describe in the Methods department and it's important information for determining whether the pseudovirus used was likely to be a good model. In another event with this newspaper, the authors as well practise not draw the "mock virus" that they used as a control or how it was constructed. As a result, I find information technology very difficult to translate their results. In fairness, some of this confusion might be considering I am non highly knowledgeable about this particular organization and don't accept the background knowledge about methodology that the authors clearly assume that the reader possesses. On the other hand, in a paper this in a journal like Circulation Research, which is not a virology journal, and especially given that this is a paper that was likely to brand the news and exist misused by antivaxxers after its release, explanatory details that let scientists from other fields with knowledge of molecular biology (but who are not experts in this field) to understand what was done are critical. A Enquiry Letter does not accomplish this.

My concerns aside, let's look at the experiments. The authors took pseudovirus or mock virus and instilled it into the tracheas of Syrian hamsters, 3 animals per experimental grouping. Some other aspect of this study defenseless my eye, namely the amount of virus used, 5 x 10viii pfu. For those of you not knowing what "pfu" stands for, it stands for "plaque-forming units." Basically it'due south a measure of the number of viable virus particles, virus particles that can infect cells and cause a plaque on a confluent layer of cells. That's half a billion particles, far, far more than of a viral challenge than the amount of virus launching any "natural" infection past SARs-CoV-ii.

Using what is a highly bogus organisation, the authors compared the levels of a whole slate of protein markers related to cell signaling and oxidative stress in the mock- and Pseu-Fasten-treated hamsters, equally well as the histology of the lungs. I won't become into detail about all of the markers examined, but rather volition step back to accept a longer view because it is non important for a lay person to empathise all the phosphorylation of this protein or ubiquitination of that poly peptide measured. (Information technology's likewise like shooting fish in a barrel to get lost in the weeds of a written report like this.) Equally stated, the authors found signs of inflammation in the alveoli (air sacs) of the Pseu-Spike-treated lungs, including thickened walls and inflammatory cells. They measured the levels of various proteins they accounted relevant:

AMPK (AMP-activated protein kinase) phosphorylates ACE2 Ser-680, MDM2 (murine double minute 2) ubiquitinates ACE2 Lys-788, and crosstalk between AMPK and MDM2 determines the ACE2 level.4 In the damaged lungs, levels of pAMPK (phospho-AMPK), pACE2 (phospho-ACE2), and ACE2 decreased only those of MDM2 increased (Figure [B], i). Furthermore, complementary increased and decreased phosphorylation of eNOS (endothelial NO synthase) Thr-494 and Ser-1176 indicated impaired eNOS activity. These changes of pACE2, ACE2, MDM2 expression, and AMPK activity in endothelium were recapitulated by in vitro experiments using pulmonary arterial ECs infected with Pseu-Fasten which was rescued past treatment with N-acetyl-L-cysteine, a reactive oxygen species inhibitor (Figure [B], two).

Translation: Compared to mock virus, Pseu-Spike altered signaling due to the ACE2 receptor, which is not surprising given that information technology's been known for a yr at present that fasten poly peptide latches onto the ACE2 receptor in order to get SARS-CoV-2 into the jail cell. As a result, there was a lower level of ACE2 in the hamster lung tissue treated with Pseu-Spike, although looking at the Western blots in Effigy 1B I am not particularly impressed by the magnitude of the decrease in protein level.

Also observed in the Pseu-Spike-treated hamster lung was decreased activity of eNOS, an enzyme that generates nitric oxide, every bit well as damage to the mitochondria, the "ability plants" of the jail cell. The authors too did the same experiments in prison cell culture alone using pulmonary vascular endothelial cells (the cells the line the inside of the arteries in the lung), reporting that they recapitulated their findings, although they used spike protein at a rather high concentration (4 μg/ml). They also tested whether similar changes occurred in vascular endothelial cells genetically engineered to make a more stable and less stable version of ACE2. They did, although this is simply suggestive, not slam dunk show, that it is the spike poly peptide-induced degradation of ACE2 that results in these intracellular changes. The authors besides reported that in pulmonary arteries isolated from the hamsters vasodilation induced by a drug called nitroprusside was not affected by Pseu-Fasten, merely the vasodilation caused by acetylcholine was dumb. Nitroprusside works by breaking down in the presence of oxyhemoglobin to produce, amongst other things, nitric oxide, while acetylcholine binds to specific protein receptors on the cell surface.

To be honest, I've never been a fan of papers this short (e.one thousand., some Nature or Science papers, which can be even shorter than this) because I can never quite figure out what the authors did; this is one of the rare cases of a paper that to me screams out for an online Supplemental Data and Supplemental Figures department, and I say this as someone who generally detests the tendency in scientific publications to dump all sorts of information into supplemental sections.

Allow's, for the sake of argument, take the results at face value and assume that this study shows what the authors say it shows, namely that spike protein damages endothelium, "manifested past impaired mitochondrial function and eNOS activity". and can cause oxidative stress that destabilizes the ACE2 receptor, leading to lower levels of the receptor. The authors themselves note that past decreasing the level of ACE2, spike protein could actually decrease the infectivity of SARs-CoV-two, given that the coronavirus needs to bind to ACE2 to become into cells, while speculating that the dysfunction of endothelial cells could outcome in endotheliitis, or inflammation of the endothelium that more than than makes up for the decreased infectivity.

But here'southward the kicker, taken correct from the final paragraph of the newspaper:

Collectively, our results propose that the S protein-exerted EC harm overrides the decreased virus infectivity. This conclusion suggests that vaccination-generated antibiotic and/or exogenous antibody against S protein not but protects the host from SARS-CoV-2 infectivity simply also inhibits Southward poly peptide imposed endothelial injury.

In other words, the vaccine could exist protective not just against infection by SARS-CoV-two but also against endothelial injury from the spike protein.

I just want to reiterate over again that this is a contrived organization. Information technology's far from a worthless system, as pseudovirus systems take value in studying the role of fasten poly peptide in the pathogenesis of COVID-19. However, given the crapton of pseudovirus used in this hamster model, I really question any relevance of this organisation to vaccine safety issues with respect to mRNA- or adenovirus-based vaccines that produce the spike poly peptide as an antigen. Why? The mRNA or adenovirus from the vaccines does not distribute extensively given that information technology's an intramuscular injection, and the spike protein is highly unlikely to attain concentrations in the circulation anywhere well-nigh the high levels produced by the model used in these experiments. Moreover, the spike protein from the vaccine is not attached in a crown-like array on a virus particle (or pseudovirus particle), but rather exists as naked unmarried poly peptide molecules, and, as has been described earlier, information technology's unclear that in this form spike protein, compared to the "crown of spikes" that gives coronaviruses their proper name, is anywhere about equally constructive at causing these downstream effects in cells. Add to that the fact that mRNA, fifty-fifty the modified mRNA in the vaccine, doesn't hang around very long and therefore doesn't generate fasten protein for very long. (Doubters should consider this: Why do the mRNA vaccines both require a second dose 3-four weeks after the first dose if, as many antivaxxers claim, the vaccines crank out spike protein indefinitely?)

Indeed, one of the authors pointed out this very outcome and took antivaxxers to job for misusing their written report:

Since I first discovered this study, it'southward just amused me how obvious it is that the antivaxxers citing this study have obviously not actually read the study itself, nor have they considered the background science and knowledge behind the study. They've merely read the press release. What do you expect, though? They're antivaxxers. This study by Uri Manor's laboratory is interesting and potentially of import because it begins to elucidate the function of the fasten protein itself in the pathophysiology of SARS-CoV-2 infection and how the spike protein lonely can cause harm, but it does not in any way propose that spike protein made by a COVID-19 vaccine is in whatsoever way toxic at the concentrations it's produced, much less that it's in any way "shed" or that the "shed" spike protein can cause disease or miscarriages in the unvaccinated who encounter the vaccinated.

Which brings me to the final of the 3 studies, which was published late last calendar week.

The deadly coronavirus spike protein produced by the Moderna COVID-nineteen vaccine?

On Friday, I started seeing a report popping up among antivaxxers. Unsurprisingly, the "pandemic's wrongest man" was all over it on Fri. His ability to misinterpret studies and thereby spread prodigious amounts of COVID-19 disinformation is depressingly impressive:

The report itself was published on May 20 in Clinical Infectious Diseases, the official journal of the Infectious Diseases Society of America (IDSA) every bit a brief report past Ogata et al, entitled "Circulating SARS-CoV-2 Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients" and is the result of a collaboration between investigators at Harvard and the University of Montreal.

The study was very straightforward in design. In cursory, investigators longitudinally studied blood samples from 13 participants who received two doses of mRNA-1273 (i.e., took samples at diverse time points after vaccination), Moderna's mRNA-based COVID-19 vaccine. I tin sum up the findings from the abstruse, namely that investigators were able to detect spike protein in the plasma of 11 of 13 participants in the trial every bit early every bit one day later on vaccination. To practice so, they used a very sensitive technique known every bit single molecule assortment (SIMOA) to detect intact spike protein and its S1 fragment produced by RNA-1273.

A brief word of the spike protein itself is in order. The fasten (South) glycoprotein of SARS-CoV-two binds angiotensin-converting enzyme-2 (ACE2) on host cells. Spike itself is processed by proteases (poly peptide-cleaving enzymes) into S1 and S2 subunits that remain associated with each other. Upon bounden to ACE2 by the spike poly peptide, the poly peptide changes conformation that leads to S1 shedding and the cleavage of S2 by host proteases. You don't really need to know the details for purposes of understanding this study, other than that spike protein has an S1 and S2 subunit, and these subunits associate with each other in the same conformation as they were before protease cleavage. This is a diagram of the construction.

SARS-CoV-2 spike protein

SARS-CoV-ii spike protein construction.

But what does the authors' finding of spike poly peptide in the plasma mean, if anything? Haven't we always been reassured that the spike protein from the mRNA vaccines doesn't get into the bloodstream and remains in cells and on the surface of the cells that produce the poly peptide after vaccination? Isn't this written report, equally antivaxxers like Berenson merits, a reason to be afraid of the Moderna vaccine, at least? The brusque answer to that terminal question is no. The longer answer follows.

We at SBM similar to repeat Paracelus' famous dictum, dosis sola facit venenum, or "only the dose makes the poison". It's a general principle of pharmacology and toxicology, namely that the dose determines the effect of a drug, or, more specifically, the concentration of any substance in the bloodstream or organs that it affects (which is related, of course, to the dose) is what matters in terms of its effects. As I like to say, even h2o can be toxic if too much is ingested. That'due south why I'll refer back to a common antivaccine trope for which I long ago coined a term, "the toxins gambit". Pre-pandemic, antivaxxers would betoken to every scary-sounding chemical they could find in vaccines and try to employ information technology as bear witness that vaccines were laden with "toxins". My favorite example is, of course, formaldehyde, which is used in the preparation of some vaccines in order to inactivate the virus used as an antigen, leaving detectable traces behind in the vaccines. I first discovered the "formaldehyde gambit" (a form of the "toxins gambit") when it was used years ago by Dr. Jay Gordon. The short version of the refutation of the "formaldehyde gambit" is to cite Paracelus and bespeak out that the corporeality of formaldehyde in any given vaccine is exceedingly small, considerably smaller than what an baby produces due to their own normal metabolism. Indeed, elevation body brunt of formaldehyde has been estimated to be less than ane% of endogenous formaldehyde.

The same thing applies to this study cited by Berenson, every bit you will see. Earlier I describe how much fasten protein the investigators establish in the plasma of these xiii study participants, allow's wait at the concentrations used, for example, in the jail cell culture experiments done by Uri Manor's group as described in the 2nd paper I discussed: 4 μg/ml.

Now, permit's expect at the "money figure" from the paper, the starting time three panels of Figure i. The reason that the authors too did the assay to notice the viral nucleocapsid poly peptide was considering the vaccine does not result in product of this protein. It was thus a negative control; unless the subject is infected with SARS-CoV-ii, nucleocapsid protein should be undetectable.

Here's the figure:

Spike protein subsequently vaccination with Moderna RNA-1273. Note the Y-axis units.

Now accept a await at the Y-axis, in particular, the units on the Y-axis: "pg/ml," or picograms per ml. That'southward 10-12 grams/milliliter. What was the concentration used by Estate's lab once again? Oh, yeah, four micrograms/milliliter . One microgram is 10-6 grams, or 1 million-fold more than than 1 picogram! Or, as Uri Manor put it:

Or, equally Ogata et al write:

S1 antigen was detected as early every bit twenty-four hours one mail service vaccination and peak levels were detected on average five days after the first injection (Figure 1A). The mean S1 peak levels was 68 pg/mL ±21 pg/mL. S1 in all participants declined and became undetectable by day fourteen. No antigen was detected at day null for 12 of 13 participants, as expected. However, one private presented detectable S1 on day nil, maybe due to analysis cross reactivity with other human coronaviruses or asymptomatic infection at the fourth dimension of vaccination. Spike protein was detectable in three of thirteen participants an average of 15 days afterwards the offset injection. The hateful fasten peak level was 62 pg/mL ± 13 pg/mL. After the second vaccine dose, no S1 or spike was detectable, and both antigens remained undetectable through day 56. For one private (Participant #8), spike was detected at twenty-four hour period 29, one twenty-four hours subsequently the second injection and was undetectable two days afterward.

Allow'southward be generous. Let'south wait at console B and examine the highest concentration of spike protein detected, which looks by the graph to have been effectually xc pg/ml. Now, for ease of calculation, let'south merely round up to 100 pg/ml every bit the highest average peak plasma concentration of spike protein after vaccination. That would still exist a 40,000-fold lower concentration than iv μg/ml. As an aside, the authors also detected IgG and IgA antibodies to spike protein and a correlation between clearance of detectable SARS-CoV-two protein and the production of IgG and IgA.

But why did Ogata et al detect any fasten protein at all? After all, we know that the fasten protein is not secreted from the cells in which it is fabricated considering information technology lacks an amino acid sequence, a so called "signal peptide sequence" that would lead to its secretion. We know that the spike poly peptide as made using the mRNA sequence template is membrane-bound, significant that information technology's embedded in the membrane of the cells that brand it. The authors speculate in the Give-and-take:

In this written report, eleven participants showroom S1 antigen in plasma after the first injection, while nucleocapsid concentrations are insignificant in all participants, confirming that the detected S1 originates from vaccination and not natural infection. The presence of S1 is likely due to the nature of the encoded mRNA-1273 spike protein, which contains a cleavable S1-S2 site and enables release of S1 from the spike trimer2. We hypothesize that release of S1 poly peptide could result from cleavage via mammalian cell proteases or circulating proteases. We detect an increase in S1 over an initial period of one to five days, suggesting that mRNA translation begins immediately after vaccine inoculation. Interestingly, spike protein appears in three of thirteen participants on boilerplate viii days after S1 is produced.

Translation: There are enzymes that tin cleave proteins (proteases), and it is possible that these proteases clipped off the S1 subunit from the spike proteins in the membrane.

Another possibility:

The Simoa antigen assays for the full spike protein are designed to require antibody binding to both the S1 and S2 subunits for detection, resulting in a broken spike protein to be undetectable. Additionally, spike protein concentrations in plasma of vaccinated participants may be beneath our assay limit of detection. We hypothesize that the cellular immune responses triggered by T-cell activation, which would occur days after the vaccination, atomic number 82 to straight killing of cells presenting spike protein and an boosted release of spike into the blood stream. The mechanisms underlying release of free S1 and the subsequent detection of the intact fasten protein remain unclear and require further studies.

In other words, some other possibility is that the immune system killing the cells producing fasten poly peptide could result in the release of enough spike protein to be detectable by this very sensitive assay. Indeed, the authors note that the detection of spike poly peptide "has non still been described in whatever vaccine study, likely due to limitations in assay sensitivity and timing cess". In other words, the authors' assay is then sensitive that information technology'south detecting incredibly minute amounts of spike protein from the vaccine in the blood that previous studies could not detect, merely because they used insufficiently sensitive assays.

As I was writing this, I was informed that an old friend Ed Nirenberg had done a similar analysis and had actually washed me one amend past comparing this written report to some other study of fasten poly peptide that reported that spike protein could impairment the claret-brain bulwark. That written report used a x nM (nanomolar) concentration of fasten protein, which, using the molecular weight of spike protein and S1 subunit and plant:

A 10 nM solution of these [fasten poly peptide and S1 subunit] would equate to xiv,610,000 pg/mL and vii,650,000 pg/mL respectively which are respectively 146100 times and 76500 times more than spike poly peptide than is found in plasma of vaccinated people.

Ed further notes:

Ah but I hear you lot protesting- the experts lied! They said no fasten circulating- clearly there'south spike circulating. Not exactly. For i thing, the information available until this point didn't show evidence of spike circulating, and we take a tendency in autograph to say that that ways there is no spike because we tin can't bear witness a negative. All assays have limits of detection (in this case it'south labelled). A x nM concentration is very small- and all the same this is still about 100,000 times more than fasten than what we find in plasma. This analysis is pretty special to be able to find anything reliably at this concentration and I would be skeptical of its accurateness at this level if not for the time points that these things are appearing. Also note that this isn't testify of spike protein being secreted past the cells that receive the mRNA, which was the cardinal consideration behind such claims and indeed based on the tiny quantities noted, that doesn't announced to be happening. The appearance of intact spike in the plasma of this admittedly small sample is very rare and transient.

Exactly. The amount of spike protein that was detected by SIMOA in this written report is low, basically not much above the current limit of detection for this poly peptide, and, more importantly, very transient. There was nothing nefarious in previous statements that spike protein from vaccines does not circulate in the bloodstream, nor was it a lie. Again, to repeat Ed, the fundamental concern was that the cells that took up the lipid nanoparticles containing the mRNA should not secrete the spike poly peptide production, which could, theoretically at to the lowest degree, actually produce a pregnant plasma concentration.

On Twitter, Alana Olgata notes that she'd like to repeat this study with other COVID-19 vaccines, which is non unreasonable:

No uncertainty antivaxxers will spring all over those papers when they are published.

The "deadly" spike protein and vaccine rubber

As I stated near the showtime of this post, antivaxxers strive mightily, higher up all, to claim that vaccines are dangerous to those receiving them and those around the recipients, all with added conspiracy theories. Information technology doesn't affair how much they have to misinterpret or misrepresent scientific studies to do and then. They'll find a way to make their misrepresentations (or failure to put studies into proper context) sound like plausible evidence that vaccines are dangerous, and they've certainly been doing this with COVID-nineteen vaccines, starting with pointing to any study that finds a role for the spike protein alone in causing cell damage. Such studies are critical to the elucidation of the molecular mechanism by which SARS-CoV-2 infects cells, replicates itself, and causes so much harm to the lungs. It'due south also of import to annotation that target effects matter. Location matters. The main infection starts in the lungs, which is where the highest concentration of virus and therefore spike protein would be expected in the case of real infections. In the case of vaccination, the location is the musculus cells of the shoulder, and whatsoever fasten protein that escapes is rapidly diluted in the bloodstream to the pg/ml range.

But what does Olgata's finding for the Moderna mean regarding the safety of the vaccine? Basically cypher. The reason is elementary. If at that place were a safety problem due to fasten poly peptide, after more than a quarter of a billion doses of vaccine administered in the US alone, there would have been rubber signal by now, given the unprecedentedly intense vaccine safety surveillance effort that accompanied the rollout of these vaccines. Recall, this is a pharmacosurveillance effort that detected literally a one-in-a-meg serious adverse outcome associated with vaccination with the Johnson & Johnson vaccine within a month and a half of its being distributed nether an emergency use authorization. It beggars the imagination to suggest that, even if the transient appearance of fasten protein after vaccination at a concentration of (at most) tens of picograms/ml were toxic, there would be no safety signal after and then many doses. It'south even more ridiculous to suggest that such a minuscule concentration of spike protein can be "shed" in quantities that could affect other people, given the incredibly low and transient concentration produced after vaccination.

Antivaxxers either don't know or understand that themselves, or they know that the vast majority of people don't know or understand that. All they need is a finding that any spike protein floats free in the bloodstream after vaccination, and they tin can employ that finding to start an effective fearfulness mongering campaign. That's exactly what they are doing now.

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Source: https://sciencebasedmedicine.org/the-deadly-coronavirus-spike-protein/

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