MemberMay 25, 2021 at 10:13 pm
The following article says that the mRNA vaccines are not causing anti-body dependent enhancement of immunity (ADE).
Why ADE Hasn’t Been a Problem With COVID Vaccines — Even with new variants, it’s unlikely antibody-dependent enhancement will be an issue
by Veronica Hackethal, MD, MSc, Enterprise & Investigative Writer, MedPage Today March 16, 2021
Early in the pandemic, scientists engaged in a flurry of discussions about the best way to construct COVID-19 vaccines to ensure their efficacy and safety. Some of these discussions centered around antibody-dependent enhancement of immunity (ADE), a potentially deadly immune phenomenon seen with other viral infections and vaccines.
So far, there have been no reports of ADE with COVID-19 vaccines. But the concerns about ADE with COVID-19 vaccines have resurfaced with the emergency of virus variants. What exactly is ADE? What do we know from past experience with it? And why do experts say it’s a non-issue with COVID-19 vaccines?
Features of ADE
While ADE can arise by different pathways, perhaps the best known is the so-called “Trojan Horse” pathway. This occurs when non-neutralizing antibodies generated by past infection or vaccination fail to shut down the pathogen upon re-exposure.
Instead, they act as a gateway by allowing the virus to gain entry and replicate in cells that are usually off limits (typically immune cells, like macrophages). That, in turn, can lead to wider dissemination of illness, and over-reactive immune responses that cause more severe illness, Barry Bloom, MD, PhD, of the Harvard T.H. Chan School of Public Health, told MedPage Today.
“The cause of ADE is having antibodies to a virus that don’t neutralize it. That enables the virus to be gobbled up by cells that have receptors for antibodies, but not the virus. That’s the way of getting virus into cells that it ordinarily would not infect,” Bloom said.
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.
What Does Past Experience Tell Us About ADE?
The classic example of Trojan Horse-style ADE comes from dengue. This virus comes in four varieties. They are different enough from each other that past infection with one does not always generate antibodies that match well enough to protect against a different variety.
ADE has also occurred after vaccination for dengue. For example, in 2016 a dengue vaccine was developed to protect against all four serotypes and given to 800,000 children in the Philippines. Among children who were vaccinated and later exposed to wild-type dengue, 14 died, presumably from more severe illness. Since then, the vaccine has been recommended only to children 9 years and older who have already been exposed to dengue.
Another classic example comes from the U.S., when ADE occurred during a clinical trial for an inactivated vaccine against respiratory syncytial virus (RSV). In 1967, children who participated in the trial and received the vaccine developed more severe RSV illness when they later encountered the virus in the community. Two toddlers died. The vaccine was associated with immune complex formation that caused lung obstruction and enhanced respiratory disease, pretty much stalling RSV vaccine development.
Similarly, cases of ADE also occurred with an inactivated measles vaccine that was being developed in the U.S. in the 1960s. After vaccinated children developed more severe illness, the vaccine was withdrawn. The live, weakened measles vaccines that are currently in use in the U.S. have not been associated with ADE.
ADE a Non-Issue With COVID Vaccines
Scientists say that ADE is pretty much a non-issue with COVID-19 vaccines, but what are they basing this on?
From the early stages of COVID-19 vaccine development, scientists sought to target a SARS-CoV-2 protein that was least likely to cause ADE. For example, when they found out that targeting the nucleoprotein of SARS-CoV-2 might cause ADE, they quickly abandoned that approach. The safest route seemed to be targeting the S2 subunit of the spike protein, and they ran with that, wrote Derek Lowe, PhD, in his Science Translational Medicine blog “In the Pipeline.”
Scientists designed animal studies to look for ADE. They looked for it in human trials, and they’ve been looking for it in the real-world data for COVID-19 vaccines with emergency use authorization. So far, they haven’t seen signs of it. In fact, the opposite is happening, Lowe noted.
“[W]hat seems to be beyond doubt is that the vaccinated subjects, over and over, show up with no severe coronavirus cases and no hospitalizations. That is the opposite of what you would expect if ADE were happening,” he wrote.
Furthermore, ADE is an acute problem, and it can be very dramatic. If it was an issue with these vaccines, we would have spotted it by now, said Brian Lichty, PhD, an associate professor in pathology and molecular medicine at McMaster University in Toronto.
“It’ll kill you quickly. In all the places I’m aware of ADE happening, it is an acute, mostly cytokine-driven event,” he told MedPage Today.
The one exception may be an inactivated whole-cell, or “killed,” vaccine developed by China. That vaccine uses alum, the same adjuvant that was used in the measles and RSV vaccines that caused ADE in the 1960s. The Chinese inactivated whole-cell vaccine could “conceivably” generate ADE like those older vaccines, according to Bloom.
“I don’t think that vaccine is ever going to see the light of day in the U.S., and it may not even be worth mentioning. There have been no actual cases of ADE with the Chinese whole-cell killed vaccine, or if so, it hasn’t been reported,” he said.
What About Variants?
Current COVID-19 vaccines were developed to protect against the original strain of SARS-CoV-2 that became dominant worldwide. As more variants arise, scientists have raised questions about whether one of these could become different enough to cause ADE. So far, that concern seems to be hypothetical, according to Lichty.
“To date, there’s really no evidence of ADE with the COVID-19 vaccines. It’s all theoretical,” he said. “I think all the evidence so far is that ADE is not turning out to be a problem with any existing vaccines or viral variants.”
One reason could be that SARS-CoV-2 just may not affect macrophages in a way that can produce ADE, although scientists are still working out the details. ADE has been reported after natural infection with other viruses, such as HIV, Ebola, and coxsackievirus, as well as other coronaviruses like SARS and MERS.
Throughout the pandemic, scientists have been looking for ADE associated with SARS-CoV-2, but so far they haven’t found any cases of it, noted Lichty.
“This coronavirus may already be sufficiently adapted to humans, so that if it does get into macrophages via a non-neutralizing antibody interaction, it may not allow the macrophage to produce enough cytokine to cause an obvious pathology,” he said.
Newer Vaccines Are Safer
Despite hesitancy about the relative newness of mRNA and adenoviral vector vaccines, these vaccines, in fact, have better safety profiles in terms of ADE than older types of vaccines, according to Bloom.
“The bottom line is that not only is the new technology faster to respond to a new viral pandemic, but so much safer and much more clearly scientifically designed,” he said. “The S protein vaccines are so much cleaner, so much more carefully defined, and so much lower risk. All you’re seeing is one protein from that virus. So the chances for ADE are much slimmer than with any of the older ways for making virus vaccines.”
Last Updated March 18, 2021
– – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – –
What is ADE?
ADE occurs when the antibodies generated during an immune response recognize and bind to a pathogen, but they are unable to prevent infection. Instead, these antibodies act as a “Trojan horse,” allowing the pathogen to get into cells and exacerbate the immune response.
Is ADE caused by a disease?
Most diseases do not cause ADE, but one of the best studied examples of a pathogen that can cause ADE is dengue virus. Dengue virus is one of the most common infections in the world, infecting hundreds of millions and killing tens of thousands of people each year. Unlike viruses like measles or mumps that only have one type, dengue virus has four different forms, called “serotypes.” These serotypes are very similar, but slight differences among them set the stage for ADE. If a person is infected by one serotype of dengue virus, they typically have mild disease and generate a protective immune response, including neutralizing antibodies, against that serotype. But, if that person is infected with a second serotype of dengue virus, the neutralizing antibodies generated from the first infection may bind to the virus and actually increase the virus’s ability to enter cells, resulting in ADE and causing a severe form of the disease, called dengue hemorrhagic fever.
Is ADE caused by vaccines?
On a few occasions ADE has resulted from vaccination:
Respiratory syncytial virus (RSV) — RSV is a virus that commonly
causes pneumonia in children. A vaccine was made by growing RSV,
purifying it, and inactivating it with the chemical formaldehyde. In
clinical trials, children who were given the vaccine were more likely to
develop or die from pneumonia after infection with RSV. As a result of
this finding, the vaccine trials stopped, and the vaccine was never
submitted for approval or released to the public.
– – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – –
But VAERS reports many coincidental (happening at the same incidence) adverse reactions and deaths. What is the theory about “triggered deaths” – are they the result of people’s immune systems rejecting the mRNA spike-protein-forming process? Is there an ANTI-ADE phenomenon where the immune system reacts OPPOSITE anti-body dependent enhancement?
Deaths Through May 14, 2021
Manufacturer Deaths Sex Deaths AGE Deaths
MODERNA 1979 M 2249 0-24 25
PFIZER\BIONTECH 1863 F 1848 25-50 249
JANSSEN 323 U 104 51-65 631
While some of these deaths are hesitantly published in VAERS as related to the receiving of injections for preventing SARS-CoV-2, the negative viewpoint of “would these people still be alive had they not been given shots” is not going to be presenting the evidence.
After a person gets a shot, there is no going back, no “antidote” to undo the effects of the solution now inside the body of the recipient.
The classic ADE definition is not being picked apart here; there is a real need to discover if “adverse effects including death” are a sign that there is a rejection by the person’s immune system that can be defined as a syndrome that would not have occurred but for the injection.
It is “legal” in the USA, perhaps wrongly, to waive the responsibility of the manufacturer, but much more, it is not right to pester people about NOT getting vaccinated if the medical researchers cannot answer the question, “do these shots trigger a reaction that makes an immune system rather die than allow being overridden with artificial instructions, i.e, do it have inate intelligence that gets so shocked by the intrusion and itself become unwilling to live?
MemberMay 25, 2021 at 10:19 pm
Sorry, I cannot fix the formatting in the discussion. The deaths should have categories as follows: manufacturer, sex, age. Then there are the deaths in each category:
Moderna, Pfizer, Janssen, Male, Female, Unknown, Age groups 0-24, 25-50, 51-65, 66-80, 81-100+.
Log in to reply.