Serious allergic reactions in at least eight people who have received the Covid-19 vaccine produced by Pfizer and BioNTech, whose first punctures in Spanish arms will be felt today, may be due to a compound in the vaccine, polyethylene glycol (PEG), says a article published in «Science». The similar mRNA vaccine developed by Moderna also contains this compound..
Until now, PEG has never been used in an approved vaccine, but it is found in many drugs that sometimes cause anaphylaxis. a life-threatening allergic reaction that can cause rashes, drop in blood pressure, shortness of breath and tachycardia.
Some allergists and immunologists believe that a small number of people previously exposed to PEG may have high levels of antibodies to PEG, which increases your risk of an anaphylactic reaction to the vaccine. “It is something feasible”, acknowledges the CSIC immunologist Matilde Cañelles. “Massive vaccinations are taking place and allergic reactions are appearing.”
In his opinion, the “huge” problem is the lack of information from the clinical trials of these two vaccines: “Scientists have not been able to access the data for these two vaccines».
However, many researchers are skeptical of this link. Still, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) called several meetings last week to discuss allergic reactions with representatives from Pfizer and Moderna, independent scientists and physicians, and the Food and Drug Administration (FDA).
NIAID is also preparing a study in collaboration with the FDA to test the response to the vaccine in people who have high levels of anti-PEG antibodies or who have previously experienced severe allergic reactions to medications or vaccines. “Until we know the possible relationship we must be very careful about speaking of that as fact,” cautions Alkis Togias of the NIAID.
From Pfizer they assure that it is «Carrying out an active follow-up of vaccinated people». In a statement sent to “Science”, the company said that it recommends that “medical treatments should always be available” in case a vaccinated person develops anaphylaxis.
Anaphylactic reactions can occur with any vaccine, but they are extremely rare, about one for every million doses, Cañelles says. But, as of December 19, in the US, six cases of anaphylaxis have already been reported among the 272,001 vaccinated people and two in the United Kingdom. “It exceeds what is usual,” he adds.
Because the mRNA vaccines from Pfizer and Moderna use a new platform, something totally new, the reactions require careful scrutiny, says the CSIC expert.
However, the communication of these cases is generating anxiety among the general population. «Patients with severe allergies are getting nervous about not being able to get vaccinated, at least with those two vaccinesTogias pointed out. “Allergies are common in the population and this information could create resistance to vaccination,” adds Janos Szebeni, an immunologist at Semmelweis University in Budapest, Hungary, and an expert in hypersensitivity reactions to PEG.
“We need to get vaccinated”
So should vaccination continue? Scientists who believe that PEG may be the culprit emphasize that vaccination must continue. «We need to get vaccinated», They say. “We have to try to reduce this pandemic.” But more data is urgently needed, he adds: “The next few weeks will be extremely important in defining what to do.”
Clinical trials of the Pfizer and Moderna vaccines, involving tens of thousands of people, found no serious adverse events caused by the vaccine. But the studies excluded people with a history of allergies to components of Covid-19 vaccines, and Pfizer also ruled out those who had previously had a serious adverse reaction to any vaccine. People with previous allergic reactions to foods or medications were not excluded, but may have been underrepresented.
Both vaccines contain mRNA wrapped in lipid nanoparticles (LNP) that help transport it to human cells and also act as an adjuvant, an ingredient in the vaccine that boosts the immune response. LNPs are «PEGilados»Chemically bonded to PEG molecules that coat the outside of the particles and increase their stability and shelf life.
PEGs are used to stabilize the drug or, in this case, the vaccine, explains Cañelles. They are also used in everyday products, such as toothpaste and shampoo., as thickeners, solvents, softeners, and moisture carriers, and have been used as laxatives for decades.
PEGs were long thought to be biologically inert, but growing evidence suggests that they are not. In fact, up to 72% of people have antibodies to PEGs, presumably as a result of exposure to cosmetics and pharmaceuticals. And at around 7%, the amount can be high enough to predispose them to anaphylactic reactions.
Meanwhile, many other scientists are not convinced that PEG is involved at all. «There is a lot of hype when it comes to the risk of PEG“Says Moein Moghimi, a researcher at the University of Newcastle (UK) who suspects that a more conventional mechanism is causing the reactions. “Technically you are administering an adjuvant at the injection site to boost the local immune system.”
Others point out that the amount of PEG in mRNA vaccines is less than in most PEGylated drugs. And while those drugs are often given intravenously, the two Covid-19 vaccines are injected into a muscle, causing late exposure and a much lower level of PEG in the blood, where most of the anti-PEG antibodies are found.
However, companies were aware of the risk. As early as 2018 Moderna recognized the possibility of “reactions.” And in a September article, the BioNTech researchers proposed an alternative to PEG for the delivery of therapeutic mRNA, noting: “PEGylation of nanoparticles can also have substantial disadvantages in terms of activity and safety.”
What can be done?
And if PEG turns out to be the culprit, what can be done? Cañelles believes that a possible solution would be not to administer the Pfizer vaccine to people with a history of allergies. “There are other vaccines, such as Moderna’s, and others that will arrive in the future.”
However, millions of people cannot be tested for anti-PEG antibodies before they are vaccinated. Instead, recommendations from the US Centers for Disease Control (CDC) recommend not administering the Pfizer or Moderna vaccines. anyone with a history of severe allergic reaction to any component of the vaccine. In people who have experienced a severe reaction to another vaccine or injectable drug, the risks and benefits of vaccination must be carefully weighed, the CDC says.
«At least [la anafilaxia] it’s something that happens quickly», Affirms Cañelles. “People who may be at high risk for an anaphylactic reaction should stay at the vaccination site for 30 minutes after injection so they can receive treatment if necessary.”
And could this compound be substituted? The CSIC expert believes that it would be possible, and it is more than likely that Pfizer is analyzing it. “Moderna’s ‘trick’ is that it uses higher concentrations of RNA, that’s why it’s more expensive, and it doesn’t need high concentrations of stabilizers like Pfizer’s. The rest of the vaccines that are under investigation will not have this problem, “he says.
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