"Fact check: COVID-19 variants come from mutations, not vaccines"
Further evidence in support of your fact check.
— 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?
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 .. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008185/ .. with viral particles, which in turn leads to worse illness.
ADE has also occurred after vaccination for dengue. For example, in 2016 a dengue vaccine .. https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-safety/antibody-dependent-enhancement-and-vaccines .. 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 .. https://cvi.asm.org/content/23/3/189 ). 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.
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 .. https://blogs.sciencemag.org/pipeline/archives/2021/02/12/antibody-dependent-enhancement-and-the-coronavirus-vaccines ."
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.
[color=red]"[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.[/color]
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."
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."
So far the Australian version of your May 31 birth date is all good. Just thought i'd let you know based on the spike protein evidence gained yesterday that all in the Australian experience is well. ;-) Let's have some good, positive, healthy fun.
World-first COVID-19 antiviral therapy developed in Brisbane and US targets virus in the body
"Fact check: COVID-19 variants come from mutations, not vaccines"
By Lexy Hamilton-Smith and staff
Posted Monday 17 May 2021 at 6:09pm, updated Tuesday 18 May 2021 at 3:36pm
VIDEO - 1m 33s Animations show how direct-acting antiviral treatment works against COVID-19.(Supplied: Griffith University)
Queensland researchers and a US team have developed an antiviral therapy that has killed off the COVID-19 viral load in infected mice by 99.9 per cent.
Key points:
* Gene-silencing RNA technology is used to destroy the COVID-19 virus genome directly and stops the virus replicating
* The treatment could be available as early as 2023, depending on the next phase of clinical trials
* The research has been published in Molecular Therapy
Lead researcher Professor Nigel McMillan, from Griffith University, called it a "seek and destroy mission" where the therapy genetically targeted the potentially deadly virus.
The international team of scientists from the Menzies Health Institute Queensland and the US research institute City of Hope began their collaborative research last April.
They used a "next-generation" viral approach using gene-silencing RNA technology to attack the virus genome directly, which stops the virus spreading.
"It causes the genome to be destroyed and the virus can't grow anymore — so we inject the nanoparticles and they go and find the virus and destroy it just like a heat-seeking missile," Professor McMillan said.
"This is the first time we have been able to package this up as a particle, send it through the blood stream to attack the virus. - "It travels to the lungs and it will actually enter all the lung cells, but only in the lung cells with the virus will it destroy — normal cells are completely unharmed by this treatment." - Professor McMillan said the treatment could be available as early as 2023.(Supplied: Griffith University)
Not a cure, but will save lives
Professor McMillan said although it was "not a cure", it was a therapy that could reduce the amount of virus in the lungs by 99.9 per cent, "so it is almost as good as a cure".
"It is really for those people who are suffering for example in ICU, where vaccines are too late," he said.
Professor McMillan said traditional antivirals like zanamivir and remdesivir reduced symptoms and helped people recover earlier.
"Where this therapy actually stops the virus replicating, so the body can repair itself and the recovery will be much quicker," he said. - "We basically should be able to eliminate people dying from this disease — if treated soon enough. - "It allows us to treat those people who are suffering from the virus who are very sick, or those who may perhaps be in danger of being exposed to the virus, such as those in hotel quarantine.
"They'd be assured they won't suffer from the disease itself."
"And any new variants that may arise in the future because it targets ultra-conserved regions in the virus's genome," Professor Morris said.
"We have also shown that these nanoparticles are stable at 4 degrees Celsius for 12 months and at room temperature for greater than one month, meaning this agent could be used in low-resource settings to treat infected patients."
Professor Kevin Morris said the treatment was designed to work on all betacoronaviruses such as SARS. (Supplied: Griffith University)
The results suggest siRNA-nanoparticle formulations could be developed as a therapy to treat COVID-19 patients, as well as used for future coronavirus infections by targeting the virus's genome directly.
"These nanoparticles are scalable and relatively cost-effective to produce in bulk," Professor Morris said.
"This work was funded as an urgent call by Medical Research Futures Fund and is the type of RNA medicine that can be manufactured locally in Australia."
Human clinical trials needed for 'promising' technology
Infectious diseases specialist Associate Professor Paul Griffin said the technology was "innovative" and "promising".
"At the moment we don't have any specific direct-acting antiviral therapies [for COVID-19], so the announcement that we've seen such a promising candidate emerge in trials at the moment is really exciting," Dr Griffin said.
He said funding was needed for more research.
"I guess we do have to keep in mind that we do need clinical trials in humans and phase one, two and three to show that it is actually effective in doing what we hope it will do and that is fighting this virus.
"It looks really effective in the animal studies, so it's a really huge step forward and it's great to see that sort of research happening in our country and our state."
Griffith University's COVID-19 antiviral research team (LtoR) Professor Kevin Morris, Dr Adi Idris, Professor Nigel McMillan, Dr Arron Supramanin and Mr Yusif Idres. (Supplied: Griffith University)
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