Free Republic
Browse · Search
General/Chat
Topics · Post Article

Skip to comments.

Science Translational Medicine mRNA Vaccines
ScienceMag.org ^ | Jan. 2021 - current | Derek Lowe, et al

Posted on 05/08/2021 9:17:52 PM PDT by Cathi

Exceptional "deep in the weeds" ongoing scientific discussion between scientists, doctors and other medical professionals about the mRNA vaccine.

Absolutely the most detailed and forthright conversation on these vaccines I have read so far.


TOPICS: Health/Medicine
KEYWORDS: herecometheqlowns; mrnavaccines
Navigation: use the links below to view more comments.
first 1-2021-4041-44 next last

1 posted on 05/08/2021 9:17:52 PM PDT by Cathi
[ Post Reply | Private Reply | View Replies]

To: Cathi

Bookmark


2 posted on 05/08/2021 9:22:02 PM PDT by sanjuanbob (Do NOT buy Chinese Products)
[ Post Reply | Private Reply | To 1 | View Replies]

To: Cathi

Thanks for posting.


3 posted on 05/08/2021 9:22:31 PM PDT by Ahithophel (Communication is an art form susceptible to sudden technical failure)
[ Post Reply | Private Reply | To 1 | View Replies]

To: All

BKMK


4 posted on 05/08/2021 9:23:37 PM PDT by BipolarBob (I'm not a thief! I said I'm a cat butler not a cat burglar.)
[ Post Reply | Private Reply | To 1 | View Replies]

To: Cathi

Bkmk


5 posted on 05/08/2021 9:24:46 PM PDT by sauropod (Chance favors the prepared mind.)
[ Post Reply | Private Reply | To 1 | View Replies]

To: Cathi

Bookmarking for later. Thanks!


6 posted on 05/08/2021 9:49:35 PM PDT by VRWCer ( Greater is He that lives in you than he who lives in the world. 1 John 4:4)
[ Post Reply | Private Reply | To 1 | View Replies]

To: Cathi

“Ten Percent for the Big Guy” Biden wants to GIVE the ChiComs and the Indians ALL the Intellectual Property, trade secrets, patents and know how needed to accomplish the vaccine production that is described in the article. He and his globalist puppet masters are determined to do this. THAT treasonous act would give the ChiComs one of the missing pieces needed to successfully engage in biological warfare. This particular piece would allow China to, in advance, manufacture, at mass production rates, mRNA vaccines for NEW viruses that they would create. They’d be able to have their population vaccinated PRIOR to releasing the new virus(es).


7 posted on 05/08/2021 10:12:22 PM PDT by House Atreides
[ Post Reply | Private Reply | To 1 | View Replies]

To: Cathi

bkmk


8 posted on 05/08/2021 10:19:48 PM PDT by Impala64ssa (Virtue signalling is no virtue)
[ Post Reply | Private Reply | To 1 | View Replies]

To: Cathi

Interesting comments. They go from this is an awesome thing to some detailed prior studies and questions about the dangers of this. You do not get a warm fuzzy feeling about this at all.


9 posted on 05/08/2021 10:27:29 PM PDT by RushingWater
[ Post Reply | Private Reply | To 1 | View Replies]

To: Cathi

Mark this


10 posted on 05/08/2021 10:28:34 PM PDT by The Mayor (I am outraged at your outrage toward the outrage!)
[ Post Reply | Private Reply | To 1 | View Replies]

To: yefragetuwrabrumuy; Wonder Warthog; metmom; Black Agnes; SunkenCiv; null and void; Swordmaker; ...
Derek Lowe can be a dick sometimes, but he's generally intellectually honest when it comes to the raw science. Thanks, Cathi!

The rest of you *PING* if you happen to be interested.

11 posted on 05/08/2021 10:37:24 PM PDT by grey_whiskers (The opinions are solely those of the author and are subject to change with out notice.)
[ Post Reply | Private Reply | To 1 | View Replies]

To: RushingWater

You read it right.


12 posted on 05/08/2021 10:47:13 PM PDT by Cathi
[ Post Reply | Private Reply | To 9 | View Replies]

To: Cathi
The comments are very good, too.

The comments by JW Ulm, MD, PhD especially seem to express the gist of what some are worried about regarding the mRNA vaccines.

Basically, he or she is concerned about exactly which cell types wind up getting "infected" with the lipids carrying the mRNA. These cells will express the spike protein, causing an immune reaction that attacks these specific cells.

If the lipids cross the blood brain barrier and cause an immune response in the brain, that's not good. He or she concludes by saying the danger will be greater if additional booster vaccinations are needed, because the immune system will once again attack the same types of cells that get "infected" by the lipids carrying the mRNA.

I would say that a lot depends here on the amount of mRNA carrying lipids that are contained in the vaccine. Even if sensitive cells are affected, if it's not too many the effects will be negligible in most cases, unless the cell "infection" causes follow on effects from the immune response like clotting. In any case, once the cells "infected" are killed off, the mRNA is gone. And it can't continue to spread once shorn of its lipid coating by infected cells because the body has lots of enzymes to destroy any mRNA floating around.

13 posted on 05/08/2021 11:17:27 PM PDT by pierrem15 ("Massacrez-les, car le seigneur connait les siens" )
[ Post Reply | Private Reply | To 1 | View Replies]

To: House Atreides; ransomnote; bitt; metmom; Black Agnes; numberonepal
Thank you.

But it's worse than that (potentially) with this virus, if you read the linked discussion.

Over-simplification by me.

It has in fact been found that mRNA from the injections doesn't stay in the injection site, but gets carried all over the body, and crosses the blood-brain barrier.

Pfizer and Moderna were real quiet about the existence or tests of any results, of tests, about the distribution of mRNA following injection.

If any brain cells express the spike protein, the immune system puts a hit out on them.

What might happen with repeated injections? Cut-and-pastes from the site from random places. PhD-level in their native language, you have been warned.

= = = = = = = =

JW Ulm, MD, PhD says: 11 January, 2021 at 5:38 pm Derek, Thank you immensely for this thorough explication on the mRNA vaccines’ lipid nanoparticles, a subject I’ve been striving to get a handle on, but this also ties into another conundrum with the vaccines that’s been raising great concern for me and lately, most of medical and biomedical colleagues: What exactly is the tissue tropism and cellular localization of these nanoparticles, and could this pose a side effect threat through errant MHC-I-mediated autoimmunity? Are they crossing the blood-brain barrier? Entering the parenchyma of vital organs (that even SARS-CoV-2 can’t access) and expressing the coronavirus spike protein on MHC-1 molecules, making these critical tissues targets of cytotoxic attack? Briefly, a major safety checkbox for the mRNA vaccine modality in general is the tissue localization of the lipid nanoparticle vehicles, for which you’ve done a wonderful job of explaining the composition of, since they are mechanistically fundamentally different from all other vaccines here. Most vaccines (what I called Type 1, e.g. subunit and inactivated virus) are essentially “MHC-2 only,” get taken up by dendritic cell phagocytosis and presented to CD4 T-cells in lymph nodes, so little to no CD8-mediated cytotoxicity against presenting cells. Attenuated virus vaccines like MMR (“Type 2”) do have some cytotoxicity mediated by CD8 lymphocytes attacking target cells presenting viral epitopes on MHC-1 cell-surface molecules, *but still limited to the tropism of the wild-type virus*. That’s where the lipid nanoparticles make mRNA vaccines elementally different from both, with a much broader tropism as far as I can tell. Even if they’re not omnitropic, it seems that they can enter a much broader tissue range compared to even attenuated virus vaccines, an impression confirmed from what you’ve written here. And since the mRNA vaccines would induce SARS-CoV-2 viral spike protein expression, that seems to mean that people who get the mRNA vaccines are going to have a much greater range of cells and tissues vulnerable to cytotoxic attack, since they’d be expressing the spike protein on MHC-I molecules. While this may prove to be more immunostimulatory, it also seems to indicate that the mRNA vaccines pose a much greater risk of systemic and critical tissue and organ damage than other vaccines, especially if multiple booster shots are needed, with side effects that may not manifest for years (with cumulative damage and chronic inflammation). This is where the picture gets aggravatingly murky, since it seems that neither Pfizer nor Moderna has posted up much of anything in the peer-reviewed literature about cellular and tissue localization from what many of us can tell, and this doesn’t seem to show up in the regulatory documents either, even though it would seem to be THE critical safety question for any proposed COVID-19 mass vaccination campaign. For the animal studies, it’d be as simple as using the companies’ nanoparticles to package GFP or equivalent indicator proteins, and seeing which tissues they go to and express the gene product. But there seems to be precious little published on this, and again from your descriptions here, it seems those tissue localizations would be quite broad. There have been published studies on LNP formulations in the past with varying tropisms but again, from what I can tell, the specific formulations in the actual vaccines are hard to get a handle on — perhaps because they’re considered trade secrets, and Pfizer and Moderna are worried about the other stealing the formula? — and even more crucially, we don’t know where in the body they’re going (through endocytosis, which leads to an MHC-1 expression pathway for viral antigens). And therefore, which tissues the vaccines’ mRNA payload is thus expressing the SARS-CoV-2 spike protein in, inviting cytotoxic attack. The nightmare scenario would be if e.g. the mRNA vaccines’ lipid nanoparticles are, indeed, crossing the BBB and getting endocytosed into critical glial cells, like oligodendrocytes, or even worse, into neurons themselves in the brain and spinal cord, putting a bullseye on these critical cells for cytotoxic CD8 lymphocytes. If so, we’d be setting the stage for a rash of multiple sclerosis and ALS-type clinical scenarios down the road with multiple boosters. My old medical colleagues have been getting especially concerned about this possibility, and I think this may be behind the recent sharp plunge in willingness among more and more healthcare workers to take the mRNA vaccines. in the absence of long-term safety or efficacy data, which is an unfortunate shortcoming given the pandemic’s urgency, we can only go with fragmented hints here and there about potential downstream issues, so we need a wealth of information with full transparency to make up for that shortcoming. And I think the recent reports of some severe adverse effects in the VAERS (esp. neurological issues, or the vaccinated Ob-Gyn physician in Miami dying suddenly of ITP that from early reports, seems to have been triggered by the vaccine) are causing cold feet among doctors and healthcare workers, esp. in the absence of tissue localization information. I used to work in gene therapy and recall how we’d obsess on tissue tropism for our vectors before considering clinical trials, so I’m bewildered that this information seems almost absent for an almost entirely new vaccine modality (for mass vaccination of healthy populations) here — it would go a long way toward reassuring fears and increasing uptake of the mRNA vaccines, both among the general public and medical professionals. As a corollary to your topic and excellent explanations here, do you happen to have information about the tissue tropism of the mRNA vaccines, specifically where the nanoparticles are going? If you’d like to do a Blog post on this, I’ll be enthusiastic to forward it on to my ex-colleagues, as there’s a massive question mark about this very issue that’s halting further vaccine adoption for a huge number of people. With better information about precisely where the mRNA vaccines are going, hopefully the concerns of health professionals especially can be reassured and boost confidence for the vaccine program. = = = = = = = =

Botond Igyarto says: 12 January, 2021 at 1:58 pm There are a lot of unknowns with this platform. I have been trying for a while to have my comments considered for publication. The furthest I got with it was that one of the top immunology journals helped me edit it to fit their requirements, and after all the efforts of trimming down they decided to drop it because the “climate is not appropriate”. Here it is, uploaded to Preprints: https://www.preprints.org/manuscript/202012.0493/v2 (or by clicking on my name). = = = = = = = =

S says: 11 January, 2021 at 8:38 pm Good information. Yes, a recent paper has been published in Nature Neuroscience entitled “The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice” to uncover its ability to cross Blood Brain Barrier. Which tissues will mRNA vaccine target exactly? A little alarming situation, this. Would be better if more information by vaccine companies are provided rather than getting anxious on trade secrets. = = = = = = = =

JW Ulm, MD, PhD says: 11 January, 2021 at 10:10 pm S, Thanks for apprising me of that paper. It helps to illuminate and builds upon many of the concerns I’ve been hearing among colleagues about potential tissue trafficking and localization. If indeed the spike protein components (as translated from the transduced vaccine mRNA) are expressed at high enough levels, this seems to raise additional questions about the potential for the gene product to cross the blood-brain barrier through adsorptive transcytosis even if expressed outside of it. This on top of the still-murky picture about whether the nanoparticles themselves can cross the BBB (or other critical tissue compartments) and enter glial cells or neurons outright, leading to expression of the cytotoxicity-inducing spike protein in complex with MHC-I on the surface of sensitive cells. Cole J. Batty (sorry can’t respond directly due to comment nesting, the commenting software doesn’t have a “Reply” option by your comment): Many thanks for providing the link to that paper. I’ve been reading as much as I can about the biochemistry and in vivo behavior of the various lipid nanoparticle formulations, and this does shed a good deal of light. However, I have to raise questions about one of the statements in your post: “The vaccines are injected intramuscularly. Blood brain barrier or organ targeting are a non-issue because this route of administration is not systemic.” This strikes me as questionable because intramuscular injection very much does lead to systemic circulation of the injected payload. In fact one of the first things we learn in med school is that IM injection is favored precisely because of the substantial vascularization of large muscles, which carries the vaccine material systemically. From the link (with my name): “Intramuscular injection is the method of installing medications into the depth of the bulk of specifically selected muscles. The basis of this process is that the bulky muscles have good vascularity, and therefore the injected drug quickly reaches the systemic circulation.” Although I agree that the vaccine’s lipid nanoparticles would likely tend to collect extensively in local lymphatics, I’ve never heard of an IM injection that’s restricted exclusively to the injection site or nearby lymphatics alone. Every time I’ve been in the clinic, IM (esp. the deltoid) has been chosen precisely because the injected material inevitably goes systemic, through which it could reach peripheral tissues, vital organs, and the blood-brain barrier. It’s still unclear of course if the vaccine is reaching the BBB, or endocytosing within glial cells or neurons beyond it, and your linked paper does help to illuminate some of the issues with trafficking and cellular localization. Still, the most challenging aspect of following the lipid nanoparticle literature is that the LNPs’ chemistry and in vivo behavior can vary so substantially depending on the specific formulation. And if the vaccine manufacturers are invoking trade secrets as a basis for withholding further details about their LNPs (or allowing independent labs to test tissue localization with reporter genes), this leaves the public with a big doughnut hole in critical knowledge about the vaccines’ in vivo behavior. Even very recent related literature on trafficking other LNPs can’t answer this question for us, since again the different lipid recipes vary so much in their chemistries and in vivo localization that we won’t know which tissues the vaccines themselves are entering. We need to have precise information regarding where exactly *the vaccine manufacturers’ specific LNPs* are going, and where the SARS-CoV-2 S protein is expressed, since a non-selective tissue localization–especially if traversing the BBB–could lead to marked cytotoxic attack on MHC-I-spike protein complexes, and thus significant cumulative tissue damage, in a range of targets potentially well beyond the localization of the wild-type virus. If anything, the wide population cohort of intended vaccine recipients, coupled with the compressed timeframe and lack of long-term efficacy and safety data, makes it all the more important to acquire such data instead of leaving such questions to chance. Even more so given the rate of adverse events and even deaths that are cropping up lately in the VAERS database logs. = = = = = = = =

Derek Lowe says: 11 January, 2021 at 10:03 pm The tissue selectivity is a good question – my immediate assumption would be that these intramuscular doses are mostly going to end up in the lymphatic system, and any that makes it into general circulation would hit the local vascular endothelium and the hepatocytes, if they make it that far. But I’ll dig into it! = = = = = = = =

JW Ulm, MD, PhD says: 11 January, 2021 at 10:58 pm Thanks Derek, a lot of us are intensively curious about anything you could find! I too had hoped off the bat that the local lymphatics would be the principal gathering site for the LNP-borne vaccine material, but in just going through my old medical school textbooks and reference lists, everything I’ve found has been pointing to one of the mantras we were taught in Year 1: An intramuscular injection (esp. in the deltoids) inevitably attains substantial systemic circulation, due to the rich vascularization of the injected tissue, and may well bypass the liver and kidneys to reach the blood-brain barrier in high volume. To expand on the quote in that resource (linked above in the reply to S and Cole’s comments), “The basis of this process is that the bulky muscles have good vascularity, and therefore the injected drug quickly reaches the systemic circulation … bypassing the first-pass metabolism.” So my back-of-the-napkin tracing of the circulatory route for a deltoid IM vaccine injection is roughly: local venules/capillaries –> cephalic vein –> axillary vein –> subclavian vein –> brachiocephalic vein –> superior vena cava –> right atrium of heart –> RV –> lungs –> LA –> left ventricle –> ascending aorta –> systemic circulation And thus from the aorta into the viscera and inferior peripheral tissues (through descending thoracic and abdominal aorta), and superiorly into the neck and head, including the brain’s blood supply through the common carotid arteries and the spinal cord (branching off from the vertebral artery in the neck). Just boiling it down — it seems from first examination that there might be considerable direct mRNA vaccine delivery to central nervous system tissues via the first couple passes, bypassing most first-pass metabolism. So then the question arises of whether the vaccines’ lipid nanoparticles would be able to traverse the BBB once at the doorstep and if so, whether they’d endocytose into oligodendrocytes and CNS neurons to express the spike protein on MHC-I complexes, or e.g. into cranial nerve (via the external carotid artery) and other PNS neurons (which could perhaps explain the Bell’s Palsy findings if these are indeed beyond the background population rate — and so on for e.g. GI and other visceral tissues.) Your excellent detailing of the LNP chemistry and adsorptive mechanisms as laid out above seems to indicate this is possible mechanistically, so from there it’s about whatever empirical data is lurking about the granular behavior of the LNPs at the BBB and other tissue barriers, which I’ve been at a loss to find. Huge thanks in advance for anything you can dig up, for all of us inquiring minds out there! = = = = = = = =

Ștefan Talpalaru says: 13 April, 2021 at 4:55 pm > my immediate assumption would be that these intramuscular doses are mostly going to end up in the lymphatic system, and any that makes it into general circulation would hit the local vascular endothelium and the hepatocytes, if they make it that far They do, and they get past the liver. Let’s look at some studies: “Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses” (2017): “Given this innovative vaccine platform, we examined the bio-distribution of the mRNA vaccines for both routes of administration. Male CD-1 mice received 6mg formulated H10 mRNA either IM or ID. Following IM administration, the maximum concentration (Cmax) of the injection site muscle was 5,680 ng/mL, and the level declined with an estimated t1/2 of 18.8 hr (Table 1). Proximal lymph nodes had the second highest concentration at 2,120 ng/mL (tmax of 8 hr with a relatively long t1/2 of 25.4 hr), suggesting that H10 mRNA distributes from the injection site to systemic circulation through the lymphatic system. The spleen and liver had a mean Cmaxof86.9 ng/mL (area under the curve [AUC]0–264of 2,270 ng.hr/mL)and 47.2 ng/mL (AUC0–264of 276 ng.hr/mL), respectively. In the remaining tissues and plasma, H10 mRNA was found at 100- to1,000-fold lower levels.” “A potent branched-tail lipid nanoparticle enables multiplexed mRNA delivery and gene editing in vivo” (2020): “IM injections yielded expression at the injection site (68%), liver (12%), and kidneys (11%). ” “Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes” (2015): “When mRNA-LNPs were injected intramuscularly and intratracheally, similar to intravenous and intraperitoneal deliveries, a large portion of the luciferase activity was detectable in the liver, demonstrating systemic spread of the nanoparticles. Also similar to intravenous and intraperitoneal deliveries, the high levels of protein produced in the liver occurred over a short duration with the majority of translation ceasing at day 2 post-injection (Fig. 2). Interestingly, significant bioluminescent signal could be measured in the lungs and muscles, as well, with the latter lasting for up to 8 days post injection.” = = = = = = = =

Marko says: 13 January, 2021 at 9:33 pm I’m not so sure it does. They equate “vaccine” with “mRNA and/or antigen”, which is not the topic of discussion. The question is, which cells pick up the LNPs after administration, rather than what happens to the mRNA/antigen produced by those cells after those target cells have been destroyed by cytotoxic cells. The paper highlighted in your link… https://www.nature.com/articles/s41551-019-0378-3 …had this to say : “A question that remains to be answered is the degree to which protein expression in the muscle is a determining factor in subsequent antigen-specific immune responses.” In other words, they didn’t investigate what happens in the muscle or other cells that take up the LNPs, instead only looking at the fate of the mRNA and the antigen subsequently produced. = = = = = = = =

Ger Dempsey says: 16 February, 2021 at 12:09 am Unfortunately I am neither an MD, a PhD holder nor a generally brilliant person but I have been following the work of Dr JW Ulm and other medics and scientists on this topic, particularly on the critical issue of NLP systemic trafficking/carrying and tissue localisation. To help you with your decision, might I suggest you follow the data from the CDC Vaccine Adverse Events Reporting System(VAERS) database which collates information on all adverse events from vaccine doses distributed thus far. I believe the database is updated and published fortnightly. https://vaers.hhs.gov/data/datasets.html? In particular, have a look at the CSV File (VAERS Symptoms) Note the references to Placenta praevia, Premature separation of placenta and Premature delivery From what I have read so far, the Pfizer vaccine is not recommended during pregnancy unless there is an over-riding risk to NOT taking it, eg a significant underlying health condition or the pregnant person is at significant high risk of contracting severe CoVid 19, in which case the balance of risks must be weighed up in consultation with your local physician and/or your OBGYN. The FDA published a briefing document titled “Vaccines and Related Biological Products” to its Advisory Committee on December 10, 2020 for the Pfizer-BioNTech COVID-19 Vaccine https://www.fda.gov/media/144245/download Page 42 of that document has a paragraph on Pregnancies and the trial participants. A New York Times article article titled “FDA may recommend against pregnant women getting Pfizer vaccine” December 11, 2020 https://nypost.com/2020/12/11/fda-may-recommend-against-pregnant-women-getting-pfizer-vaccine/ Good luck with your decision and good luck with your pregnancy. = = = = = = = =

Mandark says: 11 January, 2021 at 4:03 pm Ideally, the spike proteins should end up in specialized antigen-presenting cells, but is there anything preventing these lipid nanoparticles from entering regular cells in various tissues, leading to expression of the spike protein and eventually its presentation with MHC class I on the cell surface, marking the cells for destruction? Isn’t there any danger associated with it? A fuller version of this question was posed in this rapid response to a BMJ articicle and I haven’t seen an answer yet: https://www.bmj.com/content/371/bmj.m4037/rr-19 = = = = = = = =

JW Ulm, MD, PhD says: 11 January, 2021 at 5:27 pm I think Chemist’s point is that the lipid nanoparticles may have too broad a tropism, far broader even than attenuated virus vaccines (which are still limited to the tropism of the wild-type virus), and thus could pose a uniquely high safety hazard due to cytotoxic attack on the broad cellular range that uptakes the LNPs. Since the LNPs would enter cells via endocytosis, the SARS-CoV-2 epitopes would be expressed on MHC-1 molecules, making them targets of cytotoxic CD8 lymphocytes, attacking a much greater range of cells than any previous vaccine modality. This is concerning in general, but it’s a nightmare scenario if the vaccines are crossing the blood-brain barrier and endocytosing into e.g. oligodendrocytes (multiple sclerosis risk) or motor neurons (which could possibly cause an ALS-type picture). No other vaccine has this broad tropism. That is THE major safety concern here — been working on submitting a comprehensive question to Derek about this very topic. = = = = = = = =

Zoidberg says: 29 March, 2021 at 4:52 pm Since this article was posted, the European Medicines Agency Assesment Reports for the Moderna and Pfizer vaccines have been published, which both find some biodistribution, including across the blood/brain barrier. The Moderna study used an intramuscular injection of the same LNP as the vaccine (but a different mRNA), and found that “low levels of mRNA could be detected in all examined tissues except the kidney [, which] included heart, lung, testis and also brain tissues, indicating that the mRNA/LNP platform crossed the blood/brain barrier, although to very low levels (2-4% of the plasma level)”, with rapid clearing from most tissues. I think the Pfizer results are consistent with that: with radiolabelled LNP they found that “distribution from the [IM] injection site to most tissues occurred”, but again disproportionately more to the liver. Full details can easily be found at the European Medicines Agency. = = = = = = = =

JW Ulm, MD, PhD says:

12 January, 2021 at 8:07 am

Marko,

Excellent summary above, and as far as the follow-up safety testing you’ve hit the nail on the head with this conclusion in particular (again couldn’t reply directly above due to comment nesting):

“The question then becomes how much – 20% , 1% , .01% ? – escapes into the systemic circulation. I believe the number of RNA payloads per dose is on the order several billion, so some unknown fraction of that constitutes the number of potential off-target cells”

That’s exactly it — couldn’t have said it better. For the longitudinal follow-up in the clinical trials and broader population, it’d be helpful to have a more quantitative handle on the non-local distribution of those lipid nanoparticles distant from the injection site. I agree it wouldn’t be a huge concern if there’s just (relatively) random dispersal of injected LNPs systemically, and a nontrivial amount of hepatorenal clearance with each pass — that’s the ideal scenario. Where things get iffy are three-fold: 1. Because of the anatomy and circulatory trajectory from the deltoid and cephalic vein (essentially a straight shot into the SVC), if enough “spillover LNPs” are getting shuttled into the right atrium and transiting through the pulmonary circulation — which could be high, another reference here for the rich vasculature around IM injection — then one of their earliest stops on the map after exiting the heart would be in tissues serviced by branches of the common carotid and subclavian arteries (including the CNS), enhancing delivery to tissues behind the blood-brain barrier simply due to higher relative concentration at tissue corridors more proximal to the injection site.

2. Even if initial transit through the BBB and into other sensitive tissue parenchyma is relatively low, there’d be a cumulative effect with each booster delivering more spillover LNPs to those non-local sites. 3. Related to that point, the duration of immunity is still unclear, and there seems to be general agreement that while COVID-19 symptoms are reduced with the immunization, viral spread is not. If antibody and memory B/T-cell levels wane within a few months after vaccination, then we’d be looking at repeated boosters possibly multiple times a year given ongoing community dissemination. And since the development of many e.g. CNS disorders is gradual — with subclinical issues taking shape over years before clinical manifestations become apparent (as seen in MS and ALS) — such cumulative damage likely wouldn’t raise red flags at first, but could increase in likelihood with successive boosters.

Plus there are the potential issues raised by the paper that S dug up, such that even small levels of BBB traversal by the LNPs could engender spike protein uptake by e.g. oligodendrocytes and neurons beyond the number of LNPs themselves, due to that adsorptive transcytosis of S proteins into bystander glial and neural cells. The LNPs really are an intriguing and promising technology and it’ll be wonderful if this modality turns out to work. But simply because the clinical trial process is being accelerated so fast beyond the normal decade-long timeline for vaccine development, it just seems prudent to dot every i and cross every t when it comes to the follow-up and knowledge of the LNPs’ tissue localization, even more so given all the unknowns about the proprietary LNP formulations. In addition to animal studies with reporter genes, might be helpful to have data from more extensive imaging studies in patient cohorts, especially things like T1 and T2-weighted MRI to assess (mainly) CNS myelination and the white matter milieu in general over varying temporal intervals (3 months, 6 months, one year and so on) after receiving the injections.

14 posted on 05/08/2021 11:19:04 PM PDT by grey_whiskers (The opinions are solely those of the author and are subject to change with out notice.)
[ Post Reply | Private Reply | To 7 | View Replies]

To: pierrem15
In any case, once the cells "infected" are killed off, the mRNA is gone. And it can't continue to spread once shorn of its lipid coating by infected cells because the body has lots of enzymes to destroy any mRNA floating around.

Yes, any mRNA from the infected cells is gone. But what about the spike proteins which had been in the cell on their way to the cell wall, or the ones embedded in the cell wall which marked the poor hapless cell for the immune system to kill them?

And...there's the other matter that some medical people mentioned a day or two ago, that a cell presenting the spike protein on its surface, could have the spike protein bind to ACE2 on a neighboring cell, killing both cells?

15 posted on 05/08/2021 11:22:29 PM PDT by grey_whiskers (The opinions are solely those of the author and are subject to change with out notice.)
[ Post Reply | Private Reply | To 13 | View Replies]

To: House Atreides

“Ten Percent for the Big Guy” Biden wants to GIVE the ChiComs and the Indians ALL the Intellectual Property, trade secrets, patents and know how needed to accomplish the vaccine production that is described in the article. He and his globalist puppet masters are determined to do this. THAT treasonous act would give the ChiComs one of the missing pieces needed to successfully engage in biological warfare. This particular piece would allow China to, in advance, manufacture, at mass production rates, mRNA vaccines for NEW viruses that they would create. They’d be able to have their population vaccinated PRIOR to releasing the new virus(es).
~~~~~~~~~~~~~~~~~~

That ship has sailed. We outsourced gain of function research to Wuhan courtesy of NIH. When the Chinese were ‘done’ with gain of function research, they released a virus bioweapon which has become named Covid-19 but it’s identity is uncertain because the PCR does not test for the virus, the actual virus was not used to create the genome China ‘gave’ to us in Jan 2020, our pharma industry waited for China to give them the genome (which can’t be the correct genome based on technology used) to base the ‘vaccines’ on.

Biden is owned by China, our corrupt CDC, NIH and President are working hand in glove to benefit China after China attacked us with the China virus US tax dollars helped to development.


16 posted on 05/08/2021 11:26:14 PM PDT by ransomnote (IN GOD WE TRUST)
[ Post Reply | Private Reply | To 7 | View Replies]

To: ransomnote

I’m talking about the detailed technical knowledge required to accurately mass produce the actual mRNA vaccines. THAT intellectual property has not been given away as far as I know. You’re conflating something entirely different.

One point I was trying to make was that giving away that technology to the ChiComs would be as dangerous as giving away the technology for ICBMs to accurately deliver their nuclear payloads. And we know who did that bit of TREASON.


17 posted on 05/08/2021 11:37:02 PM PDT by House Atreides
[ Post Reply | Private Reply | To 16 | View Replies]

To: Cathi

Well, that article is terrifying.

I thought they had achieved a level of understanding of this stuff at least an order of magnitude beyond where they seem to actually be.

They have figured out that we are amazingly complex bio-supercomputers,
and they think they understand some of the programming language, but
they keep discovering remarkable new subsystems with new languages all
their own, and since they have zero liability, the world’s sheeple get to be
their experimental research subjects.

They compound their challenges to success with their “collaboration” and
non disclosures, and their drive to get rich with whatever secret sauce they
might seem to get lucky with.

As an engineer, I’m frankly appalled at their hubris.
(And it wasn’t even God, that designed the stuff I’ve worked on.)

~Easy


18 posted on 05/08/2021 11:43:36 PM PDT by EasySt (Say not this is the truth, but so it seems to me to be, as I see this thing I think I see #KAG)
[ Post Reply | Private Reply | To 1 | View Replies]

To: House Atreides

I’m talking about the detailed technical knowledge required to accurately mass produce the actual mRNA vaccines. THAT intellectual property has not been given away as far as I know. You’re conflating something entirely different.
~~~~~~~~~~~~~~~~
EVERYTHING has been given to China including the presidency, the control of the CDC and NIH.


19 posted on 05/08/2021 11:45:04 PM PDT by ransomnote (IN GOD WE TRUST)
[ Post Reply | Private Reply | To 17 | View Replies]

To: Cathi
Not all the vaccines are mRna vaccines.
Some are based om the adenovirus using old fashioned technology.
20 posted on 05/08/2021 11:51:46 PM PDT by LadyDoc (liberals only love politically correct poor people)
[ Post Reply | Private Reply | To 1 | View Replies]


Navigation: use the links below to view more comments.
first 1-2021-4041-44 next last

Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.

Free Republic
Browse · Search
General/Chat
Topics · Post Article

FreeRepublic, LLC, PO BOX 9771, FRESNO, CA 93794
FreeRepublic.com is powered by software copyright 2000-2008 John Robinson