Sasha Grams on Antibody Dependent Enhancement

Aug 18, 2021

I would like to contribute to this discussion an understanding of Antibody Dependent Enhancement that I think could help reconcile the disparate data we are hearing from multiple sources. From some sources we’re hearing that the vast majority of patients hospitalized with COVID-19 are unvaccinated. From other sources we’re hearing the majority of hospitalized patients somewhere else are vaccinated. Whether some of this data is accurate or not is another matter to sort out on a case by case basis. But the idea I wish to entertain here is that both might be true and still consistent with the march towards a wave of ADE. 

Early this spring when I first heard of cases of fully vaccinated individuals being re-exposed to the SARS-COV-2 virus I breathed a sigh of relief that they weren’t all dropping like flies of ADE. I thought perhaps we had dodged a bullet. But then I did some further reading on the subject and realized that it’s not that simple. ADE isn’t like a reaction between two chemicals under controlled conditions in a test tube. A number of factors can influence the emergence of ADE, including:

1.    Degree of affinity between the antibody and antigen

2.    Level of antibody titer (with suboptimal antibody titers predisposing to ADE)

3.    Serotype 

4.    Serostatus

5.    Age of individual

6.    Different viral strains

7.    ?possible role of vaccine adjuvants

And there may be other factors I didn’t come across in my limited review of this subject, possibly including population level and/or seasonal/ environmental factors. Ultimately, the underlying mechanism triggering ADE is a low antibody-antigen binding affinity. The antibody and antigen still have some affinity for each other in ADE but that affinity has dropped below a certain threshold at which point the antibodies become “non-neutralizing” antibodies. ADE has been described as a Trojan horse phenomenon wherein your immune system’s cells are tricked into believing that antigens (such as virions) have been neutralized when they haven’t. Then once the virus gains entry into your macrophage, for example, it is able to multiply unchecked. That is one pathway for ADE. Another mechanism of ADE involves the antigen-antibody complexes triggering an inflammatory cascade. This immunopathological reaction damages surrounding tissues. Here is a link to a brief article describing ADE with diagrams:

This might be a good article to drop in the mailbox of a colleague or physician administrator, for example.

Clinically, ADE could look like someone progressing rapidly from mild symptoms to septic shock, perhaps faster than they can even get to the ER. Or a patient might present with ARDS (Acute Respiratory Distress Syndrome) due to the inflammatory cascade triggered in their lungs. So this is a really dangerous situation to be taking a gamble on. And I hope you can see why clinicians who are aware of the possibility of ADE are VERY nervous about it.

This isn’t a remote, theoretical possibility either. ADE is such a well-known phenomenon associated with coronavirus vaccines that last fall a study was conducted to determine whether patients enrolled in clinical trials for COVID-19 vaccines were receiving adequate informed consent regarding this serious risk. The study concluded that they were not. Here is a citation for that study:

Cardozo T, Veazey R. Informed consent disclosure to vaccine trial subjects of risk of COVID-19 vaccines worsening clinical disease. Int J Clin Pract. 2021 Mar;75(3):e13795. doi: 10.1111/ijcp.13795. Epub 2020 Dec 4. PMID: 33113270; PMCID: PMC7645850.

Now, how much less informed consent is the general public receiving? I would guess the people who are aware of the risk of ADE, through their own initiative, are the same ones not taking the vaccine in most cases.

Here is another study from the journal Nature which describes the risk of ADE with coronavirus vaccines and the types of animal trials that should have been done (but weren’t) to rule out this disastrous consequence prior to these vaccines being offered to the general public.

Su, S., Du, L. & Jiang, S. Learning from the past: development of safe and effective COVID-19 vaccines. Nat Rev Microbiol 19, 211–219 (2021).

Here is an excerpt from that article:

“Meanwhile, we see two major barriers for the evaluation of safety. First, it usually takes a long time to observe VADE because it appears mainly in subsequent challenge or natural infection, by homologous or heterologous viral strains, and the occurrence is often related to antibody titres that have decreased to suboptimal levels47. Second, it is unclear whether experimental animals accurately represent human responses. From the experience and lessons derived from past development of RSV, dengue, SARS and MERS vaccines, we offer the following recommendations to developers of a safe and effective COVID-19 vaccine.

First, the safety of COVID-19 vaccine candidates should be evaluated in diverse animal models. As no animal model can accurately mimic the human immune response to vaccine candidates, evaluation in several animal models could avoid the risk of missing pathogenic responses. Second, challenge with heterogeneous viral strains should be applied in COVID-19 vaccine evaluations with antibodies cross-reactive to SARS-CoV and SARS-CoV-2 (ref.107). Third, experiments should be repeated in the same animal model at different ages. Previous studies proved that dengue vaccine performance and efficacy could be influenced by serotype, baseline serostatus and age63,68. TH2 cell-biased immunopathology was observed mainly in ageing mice immunized with inactivated SARS-CoV and alum adjuvant76.”

As this article points out, ADE can’t be expected to show up right away. To have ruled this out would have required much more time, animal studies in multiple species with multiple viral strains and repeated studies of the same animal species at different ages. Yet none of that happened prior to the commercial release of these vaccines. Now we’re just seeing what happens in the billions of people who have been injected with an experimental gene-therapy version of a vaccine that could never make it past animal studies previously.

And here is another study from 2012 which evaluated immunopathology following SARS-COV-1 vaccination in mice. This was a follow up study of immunopathology previously observed in coronavirus vaccine trials with ferrets and non-human primates. Four vaccine candidates were tested including both inactivated whole SARS virus and a recombinant DNA generated spike protein (sound familiar?) as well as a virus like particle vaccine. In all these vaccines, and across multiple species, immunopathologic reactions were ultimately observed. 

Tseng CT, Sbrana E, Iwata-Yoshikawa N, et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus [published correction appears in PLoS One. 2012;7(8). doi:10.1371/annotation/2965cfae-b77d-4014-8b7b-236e01a35492]. PLoS One. 2012;7(4):e35421. doi:10.1371/journal.pone.0035421

Here is an excerpt from the conclusion of that study:

“This combined experience provides concern for trials with SARS-CoV vaccines in humans. Clinical trials with SARS coronavirus vaccines have been conducted and reported to induce antibody responses and to be “safe” . However, the evidence for safety is for a short period of observation. The concern arising from the present report is for an immunopathologic reaction occurring among vaccinated individuals on exposure to infectious SARS-CoV, the basis for developing a vaccine for SARS. Additional safety concerns relate to effectiveness and safety against antigenic variants of SARS-CoV and for safety of vaccinated persons exposed to other coronaviruses, particularly those of the type 2 group. Our study with a VLP SARS vaccine contained the N protein of mouse hepatitis virus and Bolles, et al., reported the immunopathology in mice occurs for heterologous Gp2b CoV vaccines after challenge . This concern emanates from the proposal that the N protein may be the dominant antigen provoking the immunopathologic reaction.” (emphasis mine)

Thus, you cannot simply look at a snap shot of what’s going on in a given moment with these vaccines and conclude that because the numbers in that moment look good, therefore the vaccines are beneficial. You can’t do that when you have evidence from multiple animal trials in previous coronavirus vaccine attempts that ultimately the vaccinated animals suffered serious immunopathology on re-exposure to the wild virus (i.e. vaccine enhanced disease/ ADE). Even though the vaccine successfully generated an antibody response and some initial benefit may have been observed, the end result was worsened pathology and/ or high mortality.

Therefore, you might expect to see radically different results with the same vaccine over time. In theory, the same hospital that might be currently full of unvaccinated COVID-19 patients could end up overwhelmed with vaccinated COVID-19 patients suffering from ADE a few months from now. Could this explain what we’re seeing in Israel, one of the most vaccinated countries on earth? Early data out of Israel regarding COVID-19 mortality among the vaccinated initially looked encouraging. That is, once people made it beyond two weeks after the second shot of Pfizer. During the time from the first shot of Pfizer to two weeks after the second shot a steep rise in mortality was noted, which was concerning and the primary focus of this article. However, following that initial peri-vaccination rise in mortality, the fully vaccinated appeared to enjoy a steep drop in mortality. Here is a link to an article discussing this early data: 

So yes, there may be some evidence of short-term benefit to these vaccines. But now we have the recent data out of Israel shared by Sidney Belzberg as above. That fits with an overall trend of short-term benefits, long-term harms described in the 2012 animal study I referenced above. 

The far too short clinical trials that were done prior to the commercial rollout of our current vaccines were inadequate to rule out the dire outcome of ADE. You can’t make up for a severely truncated study timeline by injecting more people with a vaccine. If ADE emerges on a large scale in humans and the mortality rates are in the range of those seen in animal studies with prior coronavirus vaccine trials we could be looking at tens or even hundreds of millions of deaths both here in the US and around the world. If the long-term mortality rate of these vaccines due to ADE or other causes approaches 100%, which is not out of the range of what happened in some of the animal studies with prior coronavirus vaccine attempts, we could literally be looking at billions of deaths worldwide. Probably none of us want to even think about a future that horrific yet the possibility exists and has not been ruled out.

You talk about hubris, JW? Hubris is ignoring the tens of thousands of deaths already associated with these vaccines and continuing to push them on pregnant women, teenagers and children. Hubris is playing God with the human genome. Hubris is injecting billions of frightened, ill informed, unsuspecting and/ or coerced people with an experimental “vaccine”, the latest out of a long line of vaccine attempts with a horrible safety track record, just to see what happens. And if you believe this is deliberate genocide then it is the height of arrogance for someone to decide that millions or billions of other people on this planet need to die, just as long as it’s not them. That was the hubris of the Nazis. And it’s the kind of hubris that could drive our species to extinction.

I can hardly find words to describe the situation we’re in now with these vaccines. It’s a bit like watching someone drive a school bus full of children down a road littered with signs saying “Caution”, “Do Not Enter”, “Cliff Ahead”, “Turn Back Now” and instead of stopping, the crazed school bus driver is flooring it. Meanwhile the kids are in the back thinking they’re going on a field trip. Except the “kids” are billions of people and the school bus driver is a group of criminal psychopaths who have been helped all along the way by the very people who should have had the sense and courage to stop this unfolding disaster. As Dr. Tenenbaum explained in his recent article ( this COVID-19 vaccine rollout has violated every tenet of the Nuremberg Code. I’m ashamed of my profession for the role it has played in facilitating these crimes against humanity. Fortunately, the members of C19D are among the few people who are working to end this nightmare. And it’s an honor to be among them. 

 Sasha Grams, D.O.