by Bill Snyder
Vanderbilt University Medical Center is recruiting volunteers for a randomized controlled phase 2 clinical trial to help determine the prevalence of systemic allergic reactions (SARS) to the two-dose COVID-19 mRNA vaccines made by Pfizer-BioNTech and Moderna.
True allergies associated with these vaccines appear to be quite rare, in the range of only three to four cases per million doses administered, said Elizabeth Phillips, MD, an internationally known expert in drug hypersensitivity who will lead the study at VUMC.
Yet concern about safety has been cited in surveys by a significant number of people who say they are hesitant to be vaccinated. That’s why studies like this are so important, said Phillips, professor of Medicine and Pharmacology and the John A. Oates Chair in Clinical Research at VUMC.
“These mRNA vaccines could be among the safest vaccines ever developed,” Phillips said. “It is astounding that together more than 100 million doses of the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines have been administered in the United States, and we have seen almost nothing of concern regarding early safety signals.
“We really have to provide widespread reassurance to get high rates of vaccination,” she continued. “If the virus is replicating in the community, it’s going to mutate. The only way to shut that down and prevent severe illness and hospitalization is to get the population completely covered.”
VUMC is one of 30 sites participating in the SARS trial, which is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Phillips and her colleagues are seeking about 120 volunteers for the study at VUMC from the following groups:
- Healthy individuals 18 and older who have no history of severe allergic reactions and have not yet been vaccinated against COVID-19 but want to get the vaccine through their participation in the study; and
- People who are highly allergic to certain foods, drugs and other environmental triggers and who have had at least one episode of anaphylaxis requiring epinephrine injection in the past five years.
Anaphylaxis is a serious multisystem reaction that comes on rapidly and which can lead to death by asphyxiation, cardiovascular collapse and other complications. It can be reversed with no permanent effects by the timely injection of epinephrine, a hormone also used to treat asthma attacks.
Study participants will be assigned randomly to receive a first dose of one of the two mRNA vaccines or inactive placebo. The placebo group will receive the vaccine on subsequent visits.
Volunteers will be prescreened to see if they qualify for the study. They can sign up through this link or through the website of the newly formed Center for Drug Safety and Immunology at VUMC, which Phillips directs, at: https://medsites.vumc.org/centerfordrugsafetyandimmunology/cdsi-studies.
The SARS study was prompted by several cases of anaphylaxis associated with the Pfizer–BioNTech vaccine that were reported in the early rollout of the vaccine in December 2020. These cases appeared to be over-represented in individuals with an underlying allergic tendency.
As many as 2% of people who received the Pfizer-BioNTech vaccine may experience — within four hours — an “immediate reaction” such as hives, nausea, headache and other symptoms that may mimic anaphylaxis although the vast majority of these are nonallergic.
However, very few immediate reactions are due to an allergy that would rule out a second dose of vaccine, Phillips said.
The U.S. Centers for Disease Control and Prevention recommends excluding people from the mRNA vaccines if they have a history of severe or immediate allergic reaction to any vaccine component, including polyethylene glycol (PEG), which stabilizes the lipid nanoparticle that delivers the mRNA to muscle cells in the arm.
A history of anaphylaxis to food, venom or an injectable drug or vaccine that does not contain PEG or polysorbate is not a contraindication to getting the COVID-19 mRNA vaccines. However, mixed messages from the news media and vaccine centers about this can be confusing to prospective vaccinees.
“We have the background and expertise to diagnose and study PEG allergies,” Phillips said, “and as time has gone on, we’ve realized that these so-called PEG allergies, although often severe in their presentation, are quite uncommon. Most of these immediate reactions are probably not related to PEG.
“We can be reassured from our experience carefully assessing individuals with possible allergic reactions to the first dose of the Pfizer-BioNTech mRNA vaccines who have subsequently tolerated the second dose under observation in our clinics,” she said.
Still, people who experience immediate reactions require special care. At each appointment, blood samples will be taken from people in the study, including those who experience immediate reactions to vaccination, to determine if there is anything that can be measured that can reveal what is causing the reactions, Phillips said.
Recent news accounts have noted instances of Bell’s palsy, an inflammatory condition that causes a temporary weakness or paralysis of the muscles of the face, among people who received the Pfizer-BioNTech vaccine.
Association does not necessarily imply causation, Phillips cautioned. It now appears that the incidence of Bell’s palsy among those who received the vaccine is actually no higher than the rate observed in the general, unvaccinated population.
Phillips said these examples highlight the need for a robust and proactive “safety roadmap” that can uncover the mechanisms behind allergic and other adverse reactions and identify those at risk for them.
“We must be prepared to develop strategies to maximize effectiveness and safety at an individual and a population level,” Phillips and Mariana C. Castells, MD, PhD, an expert in adverse drug reactions and allergic disorders at Brigham and Women’s Hospital in Boston, wrote recently in The New England Journal of Medicine.
Minimizing hesitancy and building trust with safety data will be the key to getting populations vaccinated and controlling the pandemic, they concluded.