Scientific evidence of ADE

There has been much talk about ADE (Antibody Dependent Enhancement) from scientific skeptics of the Covid mRNA vaccine (such as Robert Malone, Luc Montagnier, et al), and a great deal of frantic censorship of their legitimate concerns by corrupt social media (Big Tech). The article on Walensky is recent and very detailed (some of it is printed below).

They’ve also been demonized and their careers ruined by snarky corrupt ‘fact-checkers’ and pundits who are paid by Big Pharma (e.g., Politifact). This only makes me believe the skeptics more, as it appears their critics have something to hide. The critics of the skeptics “doth protest too much.”

Recently, a rather conceited fellow online assured me that there’s not one shred of evidence that ADE has occurred as a result of the Covid vaccines.

Fortunately, medical journalist Sharyl Attkinsson, who looks into these things, has reported a study that seems to confirm the vaccine skeptic’s claims. Here is her article:

https://sharylattkisson.com/2021/09/exclusive-summary-covid-19-vaccine-concerns/

Attkisson states:

  • Antibody Dependent Enhancement (ADE) can make vaccinated people more susceptible to serious infection from the virus
  • “ADE may be a concern” for those who have been vaccinated for Covid-19
  • With ADE, after people get vaccinated for an initial virus, infection by a subsequent variant or strain of the virus can result in “increased viral replication and more severe disease, leading to major safety risks”
  • ADE can also “occur when neutralizing antibodies (which bind the virus and stop it from causing infection) are present at low enough levels that they don’t protect against infection. Instead, they can form immune complexes with viral particles, which in turn leads to worse illness”
  • This concern was initially described by some scientists who were subsequently banned from media platforms that incorrectly claimed the scientists were disseminating disinformation

And here is the study she refers to:
https://www.journalofinfection.com/article/S0163-4453(21)00392-3/fulltext

I am copying the whole thing here in case they take it down later. Anything it’s possible these days.

Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan/D614G strain and Delta variants. A potential risk for mass vaccination?

Highlights

  • Infection-enhancing antibodies have been detected in symptomatic Covid-19.
  • Antibody dependent enhancement (ADE) is a potential concern for vaccines.
  • Enhancing antibodies recognize both the Wuhan strain and delta variants.
  • ADE of delta variants is a potential risk for current vaccines.
  • Vaccine formulations lacking ADE epitope are suggested.

Abstract

Antibody dependent enhancement (ADE) of infection is a safety concern for vaccine strategies. In a recent publication, Li et al. (Cell 184 :4203–4219, 2021) have reported that infection-enhancing antibodies directed against the N-terminal domain (NTD) of the SARS-CoV-2 spike protein facilitate virus infection in vitro, but not in vivo. However, this study was performed with the original Wuhan/D614G strain. Since the Covid-19 pandemic is now dominated with Delta variants, we analyzed the interaction of facilitating antibodies with the NTD of these variants. Using molecular modeling approaches, we show that enhancing antibodies have a higher affinity for Delta variants than for Wuhan/D614G NTDs. We show that enhancing antibodies reinforce the binding of the spike trimer to the host cell membrane by clamping the NTD to lipid raft microdomains. This stabilizing mechanism may facilitate the conformational change that induces the demasking of the receptor binding domain. As the NTD is also targeted by neutralizing antibodies, our data suggest that the balance between neutralizing and facilitating antibodies in vaccinated individuals is in favor of neutralization for the original Wuhan/D614G strain. However, in the case of the Delta variant, neutralizing antibodies have a decreased affinity for the spike protein, whereas facilitating antibodies display a strikingly increased affinity. Thus, ADE may be a concern for people receiving vaccines based on the original Wuhan strain spike sequence (either mRNA or viral vectors). Under these circumstances, second generation vaccines with spike protein formulations lacking structurally-conserved ADE-related epitopes should be considered.The aim of the present study was to evaluate the recognition of SARS-CoV-2 Delta variants by infection enhancing antibodies directed against the NTD. The antibody studied is 1052 (pdb file #7LAB) which has been isolated from a symptomatic Covid-19 patient1. Molecular modeling simulations were performed as previously described2. Two currently circulating Delta variants were investigated, with the following mutational patterns in the NTD :

  • – G142D/E154K (B.1.617.1)
  • – T19R/E156G/del157/del158/A222V (B.1.617.2)

Each mutational pattern was introduced in the original Wuhan/D614G strain, submitted to energy minimization, and then tested for antibody binding. The energy of interaction (ΔG) of the reference pdb file #7LAB (Wuhan/D614G strain) in the NTD region was estimated to −229 kJ/mol−1. In the case of Delta variants, the energy of interaction was raised to −272 kJ.mol−1 (B.1.617.1) and −246 kJ.mol−1 (B.1.617.2). Thus, these infection enhancing antibodies not only still recognize Delta variants but even display a higher affinity for those variants than for the original SARS-CoV-2 strain.The global structure of the trimeric spike of the B.1.617.1 variant in the cell-facing view is shown in Fig. 1A. As expected, the facilitating antibody bound to the NTD (in green) is located behind the contact surface so that it does not interfere with virus-cell attachment. Indeed, a preformed antibody-NTD complex could perfectly bind to the host cell membrane. The interaction between the NTD and a lipid raft is shown in Fig. 1B, and a whole raft-spike-antibody complex in Fig. 1C. Interestingly, a small part of the antibody was found to interact with the lipid raft, as further illustrated in Figs. 1D-E. More precisely, two distinct loops of the heavy chain of the antibody encompassing amino acid residues 28–31 and 72–74, stabilize the complex through a direct interaction with the edge of the raft (Fig. 1F). Overall, the energy of interaction of the NTD-raft complex was raised from −399 kJ.mol−1 in absence of the antibody to −457 kJ.mol−1 with the antibody. By clamping the NTD and the lipid raft, the antibody reinforces the attachment of the spike protein to the cell surface and thus facilitates the conformational change of the RBD which is the next step of the virus infection process2.

Fig. 1
Fig. 1Infection enhancing antibodies recognize the NTD of Delta variants. A. Molecular model of the Delta B.1.617.1 spike trimer as viewed from the host cell surface (chains A, B and C in cyan, yellow and purple, respectively), with the NTD and RBD of each chain indicated. The 1052 antibody is in green. B. Spike trimer with the B subunit bound to a lipid raft (with 6 ganglioside GM1 molecules). C. Trimolecular [spike-antibody-raft] complex. D. Focus on the NTD-antibody complex bound to the lipid raft. E. Secondary structures of the NTD (yellow) and the antibody (green) bound to lipid raft gangliosides. F. The 1052 antibody clamps the NTD and the edge of the lipid raft.View Large ImageFigure ViewerDownload Hi-res imageDownload (PPT)

This notion of a dual NTD-raft recognition by an infection enhancing antibody may represent a new type of ADE that could be operative with other viruses. Incidentally, our data provide a mechanistic explanation of the FcR-independent enhancement of infection induced by anti-NTD antibodies1. The model we propose, which links for the first time lipid rafts to ADE of SARS-CoV-2, is in line with previous data showing that intact lipid rafts are required for ADE of dengue virus infection3.Neutralizing antibodies directed against the NTD have also been detected in Covid-19 patients45. The 4A8 antibody is a major representant of such antibodies5. The epitope recognized by this antibody on the flat NTD surface is dramatically affected in the NTD of Delta variants2, suggesting a significant loss of activity in vaccinated people exposed to Delta variants. More generally, it can be reasonably assumed that the balance between neutralizing and facilitating antibodies may greatly differ according to the virus strain (Fig. 2).

Fig. 2
Fig. 2Neutralization vs ADE balance according to SARS-CoV-2 strains.View Large ImageFigure ViewerDownload Hi-res imageDownload (PPT)

Current Covid-19 vaccines (either mRNA or viral vectors) are based on the original Wuhan spike sequence. Inasmuch as neutralizing antibodies overwhelm facilitating antibodies, ADE is not a concern. However, the emergence of SARS-CoV-2 variants may tip the scales in favor of infection enhancement. Our structural and modeling data suggest that it might be indeed the case for Delta variants.In conclusion, ADE may occur in people receiving vaccines based on the original Wuhan strain spike sequence (either mRNA or viral vectors) and then exposed to a Delta variant. Although this potential risk has been cleverly anticipated before the massive use of Covid-19 vaccines6, the ability of SARS-CoV-2 antibodies to mediate infection enhancement in vivo has never been formally demonstrated. However, although the results obtained so far have been rather reassuring1, to the best of our knowledge ADE of Delta variants has not been specifically assessed. Since our data indicate that Delta variants are especially well recognized by infection enhancing antibodies targeting the NTD, the possibility of ADE should be further investigated as it may represent a potential risk for mass vaccination during the current Delta variant pandemic. In this respect, second generation vaccines7 with spike protein formulations lacking structurally-conserved ADE-related epitopes should be considered.

References

    • Li D.
    • et al.
    In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.Cell. 2021; 184: 4203-4219View in Article
    • Fantini J.
    • Yahi N.
    • Azzaz F.
    • Chahinian H.
    Structural dynamics of SARS-CoV-2 variants: a health monitoring strategy for anticipating Covid-19 outbreaks.J Infect. 2021; 83: 197-206View in Article
    • Puerta-Guardo H.
    • Mosso C.
    • Medina F.
    • Liprandi F.
    • Ludert J.E.
    • del Angel R.M.
    Antibody-dependent enhancement of dengue virus infection in U937 cells requires cholesterol-rich membrane microdomains.J Gen Virol. 2010; 91: 394-403View in Article
    • Chi X.
    • et al.
    A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.Science. 2020; 369: 650-655View in Article
    • Liu L.
    • et al.
    Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike.Nature. 2020; 584: 450-456View in Article
    • Iwasaki A.
    • Yang Y.
    The potential danger of suboptimal antibody responses in COVID-19.Nat Rev Immunol. 2020; 20: 339-341View in Article
    • Fantini J.
    • Chahinian H.
    • Yahi N.
    Leveraging coronavirus binding to gangliosides for innovative vaccine and therapeutic strategies against COVID-19.Biochem Biophys Res Commun. 2021; 538: 132-136View in Article

Identification

DOI: https://doi.org/10.1016/j.jinf.2021.08.010

_____________________________________________________________

Director of CDC, Rochelle Walensky warns of ADE, Antibody Dependent Enhancement From Israel Data

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Director of CDC, Rochelle Walensky Warns of ADE, Antibody Dependent Enhancement From Israel Data

According to Robert Malone, MD inventor of the mRNA vaccine technology, a dreaded adverse side effect of COVID-19 vaccines is ADE, Antibody Dependent Enhancement which has been described in animal studies.(29)(31)  This is the interaction of the immune system with the virus resulting in death of most of the vaccinated animals upon re-exposure to the virus. Obviously, this is not a good thing. (16-17)

ADE Explained: Two Types of Antibodies

In this scenario, there are two types of antibodies in the experimental animals.  The first type is the neutralizing antibodies and the second type is  the enhancing antibodies.  The neutralizing antibodies are preferred since they “neutralize” or completely eliminate the virus from the body.   The enhancing antibodies are the problem since they “enhance” entry of the virus into cells, enhancing viral replication and severity of the disease.  Enhancing antibodies do exactly the opposite of the intended effect of the vaccine.  Instead of protecting the animal, the vaccine makes the viral disease worse and kills the animal.(1-15)

Previous Failed Human Vaccine Trials

Previous human vaccines against RSV and Dengue virus resulted in failed vaccine trials because of ADE, Antibody Dependent Enhancement.  In the Philippines, failure of the Dengue vaccine program led to criminal charges for researchers.  830,000 children were given the “Dengvaxia”, Dengue virus vaccine, before the program was suspended in 2017. (11-13) Dr Wen Shi Lee writes in Nature Microbiology (2020):

Previous respiratory syncytial virus and dengue virus vaccine studies revealed human clinical safety risks related to ADE, resulting in failed vaccine trials. (3) Endquote Dr. Lee

So far, with the mRNA COVID 19 vaccine, we have not seen this ADE to any appreciable degree in the US. However, early data from Israel suggests ADE is starting to appear in the vaccinated population, those who received their vaccination the earliest.

What is the significance of receiving your vaccine the earliest ? Pfizer is now recommending a third booster shot after 6 months, admitting the vaccine induced antibody protection wanes after 6 months or so. (14-15) In Australia, Dr Kerry Chant is bluntly stating everyone will need to get a booster vaccine every 6 months “forever”.  This is an obvious admission of vaccine failure. Here is Zero Hedge quoting Dr Kerry Chant, the Australian Health Minister:

“Australian health chief Dr. Kerry Chant says that COVID will be with us “forever” and people will have to “get used to” taking endless booster vaccines.” end quote

Antibodies Wane After 6 Months

As antibodies wane, the patient is now at risk for viral infection after vaccination as we have been seeing with “break through” cases.  This is the predicted scenario for ADE, and prompted Pfizer to recommend a third booster shot to avoid catastrophic ADE, as was seen with the Dengue virus in the Philippines.(1-15)

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Ungekrzte

"Enlightenment is man's emergence from his self-imposed immaturity ... the inability to use one's own understanding without another's guidance. This immaturity is self-imposed if its cause lies not in lack of understanding but in indecision and lack of courage to use one's own mind without another's guidance. Dare to know! (Sapere aude.) "Have the courage to use your own understanding," is therefore the motto of the [European] Enlightenment. "Laziness and cowardice are the reasons why such a large part of mankind gladly remain minors all their lives, long after nature has freed them from external guidance. They are the reasons why it is so easy for others to set themselves up as guardians. It is so comfortable to be a minor. If I have a book that thinks for me, a pastor who acts as my conscience, a physician who prescribes my diet [or vaccine], and so on--then I have no need to exert myself. I have no need to think, if only I can pay; others will take care of that disagreeable business for me. Those guardians who have kindly taken supervision upon themselves see to it that the overwhelming majority of mankind ... should consider the step to maturity, not only as hard, but as extremely dangerous. First, these guardians make their domestic cattle stupid and carefully prevent the docile creatures from taking a single step without the leading-strings to which they have fastened them. Then they show them the danger that would threaten them if they should try to walk by themselves. Now this danger is really not very great; after stumbling a few times they would, at last, learn to walk. However, examples of such failures intimidate and generally discourage all further attempts. "Thus it is very difficult for the individual to work himself out of the immaturity which has become almost second nature to him. He has even grown to like it, and is at first really incapable of using his own understanding because he has never been permitted to try it. Dogmas and formulas [e.g., Leftist ideology, identity politics] these mechanical tools designed for reasonable use--or rather abuse--of his natural gifts, are the fetters of an everlasting immaturity. The man who casts them off would make an uncertain leap over the narrowest ditch, because he is not used to such free movement. That is why there are only a few men who walk firmly, and who have emerged from immaturity by cultivating their own minds." - Kant, "An Answer to the Question: What is Enlightenment"

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