The two Covid-19 vaccines, blocked by potential side effects, have one thing in common: both are based on adenoviruses, cold germs that researchers have used for decades in experimental therapy with different results.
Johnson & Johnson said late Monday that they would suspend a trial to investigate a disease he did not specify in one of the study participants. Meanwhile, The vaccine, which she is developing with Oxford University, was tested by AstraZeneca Plc in the United States. stopped by regulators more than a month after the onset of neurological symptoms in two volunteers.
With AstraZeneca in the pit stop, the vaccine from Modern Inc. and Pfizer Inc.-The BioNTech SE partnership took the lead in the race, coming out first. Meanwhile, two suspended trials raise questions about adenoviral vectors, which have been used for years in laboratory, animal, and human experiments. In some cases, the experiments were successful, but not always.
And this year, as Covid-19 vaccines become a part of politics, transparency and trust are key to fighting the virus, which has affected more than 39 million people worldwide and disrupted the economy. If concerns about side effects in experimental vaccines in trials using adenoviruses are confirmed, it may increase skepticism in the general public and raise issues for other drug manufacturers.
“While this may be a coincidence,” says Sam Fazeli, a Bloomberg Intelligence analyst, in a research note, “adenoviral vector vaccines are more likely to have a higher risk of rare side effects – such as autoimmune attacks such as transverse myelitis – than in Pfizer-BioNTech, Moderna or Novavax “.
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Pauses to study side effects are not uncommon for vaccine trials that require a high level of safety because they are taken by healthy people. Oxford said there was not enough evidence to link the participants’ illnesses to the vaccine. Tests on humans in the UK, South Africa and Brazil resumed a few weeks ago.
Adenovirus vectors are well studied, universal and well tolerated, making them good candidates for Covid vaccines, according to AstraZeneca in an email. Reactions to the Astra / Oxford vaccine in early studies were comparable to those found in previous trials of other vaccines using adenoviruses, the company said. Oxford researchers declined to comment.
In some cases, experiments using adenoviruses have been successful. For example, earlier this year, the J&J vaccine was based in part on adenovirus Approved to fight Ebola, which has killed thousands in Africa.
However, in other experiments there were disappointing results. In 2008, a vaccine using adenovirus was developed Merck & Co. to prevent HIV was tied an increase in the number of infections among those who received it during the trials. Merck dropped the shot, and several similar programs fell into the background.
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If researchers determine in current trials that the cause of the episodes is related to vaccines, they will look for potential links to the adenoviral approach, as well as to the protein that the vaccine is designed to prepare the immune system for a real infection, according to Michael Kinch, a vaccine specialist. at the University of Washington in St. Louis.
At the moment, he said, there is not enough information to know. “Is this just a random chance?” said Kinch. “First of all, there is misfortune. If it turns out that there is a relationship and a causal relationship, the conversation turns very quickly. “
J&J stated that it was still learning about the trial participant’s illness. According to Paul Stoffels, the company’s chief research officer, Paul Stoffels, the adenovirus in the Covid experimental shot has been used by more than 110,000 people worldwide.
“We are very quickly relying on a very large carrier safety database,” Stoffels said in an interview before the trial was adjourned.
Discovered in human adenoids in 1953, adenoviruses have a number of drug-delivery features. Although some infect human cells easily, in most cases they cause only minor symptoms. Strains that appear in different animals, such as cows and chimpanzees, can be adapted for different purposes, such as veterinary vaccines.
Best of all, it was relatively easy for scientists to mix and match the genes within them, offering a variety of features and properties.
“You take out genes that control the virus’s ability to proliferate,” said Ron Crystal, a medical researcher at Weill Cornell in New York who pioneered the use of adenoviruses as vectors, “and make their genes.”
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Viruses naturally add their genomes to cells, causing them to produce viral proteins. In the 1990s, researchers added genes to the adenovirus to create an enzyme that was not present in the genetic disorder.
The idea was that infected cells would produce an enzyme to cure the disease. Instead, the first patient treated in this way died of a severe immune reaction.
“We didn’t realize how immunogenic these viruses were,” Crystal said.
The tragic death has been a failure for gene therapy, which has only revived in the last few years, when a number of potentially rescue therapies have been approved, and even more are being tested.
Meanwhile, drug and vaccine developers have continued to develop vaccines around much lower doses of adenoviruses. When used in smaller amounts, the immune response to adenovirus “is not a problem,” according to Crystal. If anything, vaccine developers see the body’s immune response as a potential advantage, he said.
“They essentially act as an adjuvant, and it boosts the immune response,” to the vaccine, Crystal said.
Existing human immunity to chimpanzee adenoviruses, such as that used in the Oxford vaccine, is less of a concern, said Lindsey Baden, an infectious disease specialist at Harvard-affiliated Brigham and Women’s Hospital in a podcast sponsored by New England Journal of Medicine.
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However, with such new technologies, “safety is difficult to know,” said Baden, who has worked in the vaccine industry for decades. “If you studied it in 1,000 people, you don’t know the risk of 1 in 10,000; if you studied it in 10,000 people, you don’t know 1 in 100,000, etc. “
If adenoviruses are associated with side effects that have occurred in Covid vaccines, it may stop the development of many projects, as has been done with HIV and gene therapy. According to data, there are more than a dozen Covid vaccines based on adenoviruses World Health Organization.
If investigators determine in current trials that the cause of the episodes is related to vaccines, they will look for potential links to the adenoviral approach, as well as to the protein that the vaccine is designed to prepare the immune system for a real infection, according to Kinch of the University of Washington.
At the moment, he said, the information is not enough to know. “Is this just a random chance?” said Kinch. “First of all, there is misfortune. If it turns out that there is a relationship and a causal relationship, the conversation turns very quickly. “
– With the assistance of Robert Langret, Susie Ring and Riley Griffin