News & Politics

Nanoparticles May Be the Culprit in Rare COVID Vaccine Allergic Reactions

AP Photo/Jessica Hill

Scientists may be zeroing in on what has caused severe allergic reactions in at least six people who have received a dose of Pfizer’s COVID vaccine. Both the Pfizer and Moderna vaccines contain tiny nanoparticles of PEG —  polyethylene glycol. The manmade compound is used as part of the packaging of the messenger RNA. PEG helps carry the vaccine to human cells and also acts as a boost to our immune response.

Allergic reactions to vaccines are expected to be one in a million doses. But the Pfizer vaccine experienced six such allergic reactions in just 272,000 patients.


PEG has never been used before in an approved vaccine, but it is found in many drugs that have occasionally triggered anaphylaxis—a potentially life-threatening reaction that can cause rashes, a plummeting blood pressure, shortness of breath, and a fast heartbeat. Some allergists and immunologists believe a small number of people previously exposed to PEG may have high levels of antibodies against PEG, putting them at risk of an anaphylactic reaction to the vaccine.

Others are skeptical of the link. Still, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) was concerned enough to convene several meetings last week to discuss the allergic reactions with representatives of Pfizer and Moderna, independent scientists and physicians, and the Food and Drug Administration (FDA).

“Until we know there is truly a PEG story, we need to be very careful in talking about that as a done deal,” says Alkis Togias, branch chief of allergy, asthma, and airway biology at NIAID. That’s very good advice. There may be a variety of reasons for an allergic reaction or perhaps a combination of factors. Anaphylaxis is a severe response of the immune system and there are many factors that could trigger it.

PEG is in many household products we use every day — toothpaste and shampoo to name two. They’re used as thickeners, solvents, softeners, and moisture carriers, and they’ve been used as a laxative for decades. But why PEG triggers an immune response is a mystery.

Szebeni says the mechanism behind PEG-conjugated anaphylaxis is relatively unknown because it does not involve immunoglobulin E (IgE), the antibody type that causes classical allergic reactions. (That’s why he prefers to call them “anaphylactoid” reactions.) Instead, PEG triggers two other classes of antibodies, immunoglobulin M (IgM) and immunoglobulin G (IgG), involved in a branch of the body’s innate immunity called the complement system, which Szebeni has spent decades studying in a pig model he developed.

Why didn’t Pfizer discover the adverse reaction before this? Apparently, in setting up their trials, the company excluded people who were allergic to vaccines in general and allergic to the ingredients found in the serum.

But Pfizer was aware of a potential problem with PEG.

Nevertheless, the companies were aware of the risk. In a stock market prospectus filed on 6 December 2018, Moderna acknowledged the possibility of “reactions to the PEG from some lipids or PEG otherwise associated with the LNP.” And in a September paper, BioNTech researchers proposed an alternative to PEG for therapeutic mRNA delivery, noting: “The PEGylation of nanoparticles can also have substantial disadvantages concerning activity and safety.’”

Where does that leave millions of people who want the vaccine? Ultimately, It’s up to the FDA, which may recommend that anyone who gets the vaccine stay close to the doctor’s office for 30 minutes. An anti-body test of those who think they may be allergic to PEG may also be recommended.

While the number of adverse reactions to the vaccine is still very low, it doesn’t do anything for the confidence of the American people, regarding the safety of the vaccine, to know that some people are having problems after being dosed.