Scientific researchers are eyeing a potential culprit in the allergic reactions to Pfizer Inc.’s PFE -0.45% and BioNTech SE’s BNTX -3.10% Covid-19 vaccine: the compound polyethylene glycol, also widely known as PEG.
There have been six reported severe allergic reactions to the vaccine in the U.S., according to the Centers for Disease Control and Prevention, out of 272,001 doses administered through Dec. 19. There have also been at least two cases of anaphylaxis in the United Kingdom. People in the U.S. began receiving the vaccine from Moderna Inc. on Monday, and so far no allergic reactions to it have been reported.
Pfizer made a statement saying it will “closely monitor any reports suggesting serious allergic reactions following vaccination.” It said its prescribing information includes a warning that “appropriate medical treatment and monitoring should always be available in the event of a rare anaphylactic event following administration of the vaccine.”
Researchers have targeted PEG as a possible suspect, although health officials say they are still investigating the incidents and plan to look into the issue further. That compound is found in other medications and can cause anaphylaxis in rare cases.
“Although I think we’re just speculating here…it is known that one of the components that is present in both of the vaccines-polyethylene glycol-may be associated, rarely, with allergic reactions,” said Peter Marks, director of the Food and Drug Administration Center for Biologics Evaluation and Research, at a Dec. 18 news conference.
“What we’re learning now is that these allergic reactions might be somewhat more common than the very rare ones that we thought they were because people are getting polyethylene glycol in various pharmaceutical preparations,” and he said, noting that the FDA also plans to watch the Moderna vaccine rollout “very closely” since both vaccines contain PEG.
PEG in both the Pfizer-BioNTech and Moderna vaccines is part of the lipid envelope that surrounds messenger RNA, the main ingredient in the vaccine. Once the mRNA enters the cells, it teaches them to make a protein similar to the spike protein on the surface of the coronavirus. As a result, it triggers a specific immune response that boosts the body’s defenses when the body is exposed to the real virus. The fat coat containing PEG ensures that the mRNA passes through the cell membrane and into the cells.
Allergies against PEG are extremely rare, allergists and immunologists say, and it’s possible that the few people who had reactions after being vaccinated with the Pfizer BioNTech vaccine were reacting to something else. However, the compound is found in a number of products, including cosmetics, foods, and medications. Some vaccines also contain PEG-like compounds, they note.
There are some types of PEG that are more likely to cause allergic reactions than others, the scientists say.
“They’re all in one big family, but they’re not the same in terms of allergic potential,” says Elizabeth Phillips, director of the Center for Drug Safety and Immunology at Vanderbilt University Medical Center. Types of PEG that are more severe are generally more likely to cause allergic reactions than others, she noted.
Meanwhile, “the PEG in the vaccines is different than what has been previously associated with allergic reactions,” said James Baker, an immunologist who directs the Michigan Nanotechnology Institute for Medicine and the Biological Sciences at the University of Michigan.
“The overall structure is very different than anything that’s been in a vaccine before,” he stated. Making it hard to tell how allergic reactions to the PEG in the Covid-19 vaccines will compare to allergic reactions to other PEGs, such as those in certain laxatives that have caused rare allergic reactions in the past.
Experts in allergy say it is not yet certain whether the reactions observed so far are classic allergic reactions – that is, immune reactions involving an antibody called immunoglobulin E (IgE), which is part of the so-called adaptive arm of the immune system that learns to recognize certain invaders. The reactions could also be due to a misfiring of the innate immune system, which triggers a cascade of reactions in the body’s so-called complement system.
“We need to consider all possibilities,” Dr. Baker says.
He and Dr. Phillips both recently participated in a virtual meeting hosted by the National Institute of Allergy and Infectious Diseases to discuss allergic reactions to the Covid 19 vaccine. Officials at the agency said they plan to conduct a study to look more closely at the problem.
“We anticipate studying highly allergic individuals with previous episodes of anaphylaxis, as well as some other groups such as patients with known PEG allergy,” Daniel Rotrosen, director of the Division of Allergy, Immunology and Transplantation at NIAID, said in an email. The study will also include healthy individuals for comparison, he said, and researchers will collect biological samples before and after vaccination to monitor any immune changes induced by the vaccine.
And while PEG is a possible culprit, “we need to keep an open mind about other possibilities,” he added.
As for now, the CDC says that people who have a history of severe allergic reactions to any component of the Pfizer-BioNTech or Moderna vaccines should not receive the vaccine, and those who have a severe allergic reaction after the first dose should not receive the second.
Individuals with severe allergies to other vaccines or injectables can receive the vaccine, but should talk to their doctor beforehand to weigh the risks of an allergic reaction against the benefits of the vaccine, the agency advises.
There is no reason why people who have a history of mild or severe allergic reactions to foods, pets, oral medications or environmental allergens should not receive the vaccine, the CDC says.
The agency also says people who get the shots should be observed for 15 minutes after vaccination to watch for possible adverse reactions. People with a history of anaphylaxis should be observed for 30 minutes, it says.
The FDA requires that appropriate medical treatment for allergic reactions be available immediately in the event of an acute anaphylactic reaction.