(STUDY) Why So Many Vaccinated People Get Sick: Antibody Dependent Enhancement (ADE)

According to studies:

• ADE may make vaccinated people more susceptible to serious infection with the virus
• “ADE may be a concern” for those who have been vaccinated against Covid-19
• With ADE, once people have been vaccinated against an initial virus, infection with a later variant or strain of the virus can lead to “increased viral replication and more serious disease, leading to major risks to the virus. security”
• ADE can also “occur when neutralizing antibodies (which bind to the virus and prevent it from causing infection) are present at levels low enough that they do not protect against infection. Instead, they may forming immune complexes with viral particles, which in turn leads to worse disease “
• This concern was originally described by some scientists who were later banned from media platforms who falsely claimed that scientists were disseminating disinformation.
• Scientists in the study suggest the answer is to create a new vaccine

In a new study by Journal of infections, scientists explain a likely reason why so many vaccinated people get sick: a dangerous phenomenon called Antibody Dependent Enhancement or ADE.

Despite the fact that several medical authorities predicted, told us and hoped that ADE would not impact Covid-19 vaccines, study data indicates that it did just that.

According to the new study, the data suggests that the Covid-19 vaccines originally appeared to offer an overall advantage in the fight against the virus. However, with respect to one of the new iterations of Covid, the Delta variant, the vaccines appear to facilitate infection by displaying “a remarkably increased affinity” for the virus’ branded spike protein.

Scientists conclude that “ADE may be of concern” for those who have been vaccinated against Covid-19.

Read the study here.

According to a scientific study, the risk of ADE was well known before Covid-19 vaccines were allowed on the market.

“A potential hurdle for vaccines and antibody-based therapies is the risk of exacerbating the severity of COVID-19 via antibody-dependent enhancement (ADE),” a study explained in Nature. “ADE can increase the severity of several viral infections, including other respiratory viruses such as respiratory syncytial virus (RSV) and measles.”

Scientists say that with ADE, once people get vaccinated against an initial virus, infection with a later variant or strain of the virus can lead to “increased viral replication and more serious disease, resulting in major security risks “.

“Non-neutralizing antibodies generated by a past infection or vaccination fail to stop the pathogen upon re-exposure. Instead, they act as a gateway by allowing the virus to enter and replicate in cells that are generally off limits … This, in turn, can lead to a wider spread of the disease and overly reactive immune responses that cause more serious disease, ”the scientists say.

A MedPage article (before the new study) dismissed concerns about ADE, but noted that it “can also occur when neutralizing antibodies (which bind to the virus and prevent it from causing infection) are present at levels low enough that they do not protect against infection. Instead, they can form immune complexes with viral particles, which in turn worsens the disease. “

In contrast, most scientific studies on this subject indicate that those who have recovered from Covid-19 have natural immunity that does not present the same problem, and appears to be superior to that, so far, that provided by vaccines.

Still, the Centers for Disease Control (CDC) and many public health officials are pushing for more people to get vaccinated, including those who have already been infected with Covid. (Numerous studies suggest that there is no benefit in cured patients getting vaccinated.) Health officials say vaccinated patients who receive Covid have milder forms than if they did not. not been vaccinated. However, this is a case-by-case assumption and it is impossible to prove it.

In Israel, health officials say only 1% of Covid infections in the latest wave are among those previously infected with Covid. The remaining 99% are among the unvaccinated and uninfected previously, and among the fully vaccinated.

According to the new study, the solution to the current ADE problem is to invent a new, updated version of the vaccine.

Learn more about the new study below:

Antibody-dependent improvement (ADE) of infection is a safety concern for vaccine strategies. In a recent publication, Li et al. (Cell 184: 1-17, 2021) reported that infection-promoting antibodies directed against the N-terminal domain (NTD) of the SARS-CoV-2 spike protein facilitate viral 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 by Delta variants, we analyzed the interaction of facilitating antibodies with the ATNs of these variants. Using molecular modeling approaches, we show that activator antibodies have a higher affinity for Delta variants than for Wuhan / D614G NTDs. We show that the enhancer antibodies enhance the binding of the tip trimer to the host cell membrane by binding the NTDs to the microdomains of the lipid raft. This stabilization mechanism may facilitate the change in conformation which induces the unmasking of the receptor binding domain. As 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 neutralizing the original Wuhan / D614G strain. However, in the case of the Delta variant, the neutralizing antibodies have a reduced affinity for the spike protein, while the facilitator antibodies show a remarkably increased affinity. Thus, ADE may be of concern to people receiving vaccines based on the spike sequence of the original Wuhan strain (either mRNA or viral vectors). Under these circumstances, second generation vaccines with advanced protein formulations lacking structurally conserved epitopes linked to ADE should be considered. The aim of the present study was to evaluate the recognition of variants of SARS-CoV-2 Delta by infection-increasing antibodies directed against NTD. The antibody studied is 1054 (pdb file # 7LAB) which was isolated from a patient symptomatic of Covid-19¹. Molecular modeling simulations were performed as described previously². Two Delta variants currently in circulation were studied, with the following mutational patterns in NTD:

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

Each mutational model was introduced into the original Wuhan / D614G strain, subjected to energy minimization, and then tested for antibody binding. Interaction energy (ΔG) from reference bp file # 7LAB (Wuhan / D614G strain) in the NTD region was estimated to be -229 kJ / mol^-1. In the case of the Delta variants, the interaction energy has been increased to -272 kJ.mol^-1(B.1.617.1) and -246 kJ.mol^-1 (B.1.617.2). Thus, these infection-increasing antibodies not only still recognize the Delta variants, but even display a higher affinity for these variants than for the original strain of SARS-CoV-2. The overall structure of the trimeric tip of the B.1.617.1 variant in the cell – the front view is shown in Figure 1A. As expected, the NTD-bound facilitator antibody (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 membrane of the host cell. The interaction between NTD and a lipid raft is shown in Figure 1B, and a whole raft-spike-antibody complex in Figure 1VS. Interestingly, a small portion of the antibody was found to interact with the lipid raft, as shown in more detail in Figures 1.OF. Specifically, two distinct loops of the heavy chain of the antibody, encompassing amino acid residues 28-31 and 72-74, stabilize the complex through direct interaction with the lipid raft edge (Figure 1F). Overall, the interaction energy of the NTD-raft complex increased from -399 kJ.mol^-1 in the absence of the anti-457 kJ.mol antibody^-1 with the antibody. By binding the NTD and the lipid raft, the antibody enhances the binding of the spike protein to the cell surface and thus facilitates the conformational change of RBD which is the next step in the viral infection process.².