They should not deter people from becoming vaccinated
Stanford Medicine
The
findings published online in JAMA Network Open.
"We
wanted to understand the spectrum of allergies to the new vaccines and
understand what was causing them," said the study's senior author, Kari
Nadeau, MD, PhD, the Naddisy Foundation Professor in Pediatric Food Allergy,
Immunology, and Asthma.
The
study analyzed 22 potential allergic reactions to the first 39,000 doses of
Pfizer and Moderna COVID-19 vaccines given to health care providers at Stanford
soon after the vaccines received emergency use authorization from the Food and
Drug Administration.
Most
of those in the study who developed reactions were allergic to an ingredient
that helps stabilize the COVID-19 vaccines; they did not show allergies to the
vaccine components that provide immunity to the SARS-CoV-2 virus. Furthermore,
these allergic reactions occurred via an indirect activation of allergy
pathways, which makes them easier to mitigate than many allergic responses.
"It's nice to know these reactions are manageable," said Nadeau, who directs the Sean N. Parker Center for Allergy and Asthma Research at Stanford. "Having an allergic reaction to these new vaccines is uncommon, and if it does happen, there's a way to manage it."
The
study's lead author is former postdoctoral scholar Christopher Warren, PhD, now
an assistant professor at Northwestern University Feinberg School of Medicine.
The
research also suggests how vaccine manufacturers can reformulate the vaccines
to make them less likely to trigger allergic responses, Nadeau said.
Delivery
of protein-making instructions
The mRNA-based COVID-19 vaccines provide immunity via small pieces of messenger RNA that encode molecular instructions for making proteins. Because the mRNA in the vaccines is fragile, it is encased in bubbles of lipids -- fatty substances -- and sugars for stability.
When the vaccine is injected into someone's arm, the
mRNA can enter nearby muscle and immune cells, which then manufacture
noninfectious proteins resembling those on the surface of the SARS-CoV-2 virus.
The proteins trigger an immune response that allows the person's immune system
to recognize and defend against the virus.
Estimated
rates of severe vaccine-related anaphylaxis -- allergic reactions bad enough to
require hospitalization -- are 4.7 and 2.5 cases per million doses for the
Pfizer and Moderna vaccines, respectively, according to the federal Vaccine
Adverse Event Reporting System. However, the federal system doesn't capture all
allergic reactions to vaccines, tending to miss those that are mild or
moderate.
For
a more complete understanding of allergic reactions to the new vaccines -- how
common they are, as well as how severe -- the research team examined the
medical records of health care workers who received 38,895 doses of mRNA-based
COVID-19 vaccines at Stanford Medicine between Dec. 18, 2020, and Jan. 26,
2021. The vaccinations included 31,635 doses of the Pfizer vaccine and 7,260
doses of the Moderna vaccine.
The researchers searched vaccine recipients' medical records for treatment of allergic reactions and identified which reactions were linked to the vaccines. Twenty-two recipients, 20 of them women, had possible allergic reactions, meaning specific symptoms starting within three hours of receiving the shots.
The researchers looked for the following symptoms in recipients' medical records: hives; swelling of the mouth, lips, tongue or throat; shortness of breath, wheezing or chest tightness; or changes in blood pressure or loss of consciousness.
Only 17 of the 22 recipients had reactions that met diagnostic
criteria for an allergic reaction. Three recipients received epinephrine,
usually given for stronger anaphylaxis. All 22 fully recovered.
Of
the 22 recipients, 15 had physician-documented histories of prior allergic
reactions, including 10 to antibiotics, nine to foods and eight to
nonantibiotic medications. (Some recipients had more than one type of allergy.)
The
researchers performed follow-up laboratory testing on 11 individuals to
determine what type of allergic reaction they had, as well as what triggered
their allergy: Was it one of the inert sugar or lipid ingredients in the
bubble, or something else in the vaccine?
The
study participants underwent skin-prick tests, in which a clinician injected
small amounts of potential allergens -- the lipids, sugars (polyethylene glycol
or polysorbates) or entire vaccine -- into the skin. Skin-prick testing detects
allergic reactions mediated by a form of antibody known as immunoglobin E, or
IgE; these reactions are generally associated with the severest allergies.
None
of the recipients reacted on skin-prick tests to the inert ingredients in the
vaccines, and just one recipient's skin reacted to the whole COVID-19 vaccine.
Follow-up blood tests showed that the vaccine recipients did not have
significant levels of IgE antibodies against the vaccine ingredients.
Since the skin tests did not explain the mechanism of recipients' allergic reactions, the investigators proceeded to another type of diagnostic test. Vaccine recipients provided blood samples for tests of allergic activation of immune cells known as basophils.
The blood samples from 10 of the 11 participants
showed a reaction to the inert ingredient polyethylene glycol (PEG), which is
used in both the Pfizer and Moderna vaccines. In addition, all 11 recipients
had basophil activation in response to the whole mRNA vaccine when it was mixed
with their own basophils.
All
11 subjects had high levels of IgG antibodies against PEG in their blood; IgG
antibodies help activate basophils under some conditions, and this finding
suggests the individuals were likely sensitive to PEG before receiving their
vaccines.
"What's
important is what we didn't find, as much as what we did find," Nadeau
said. "It does not seem that the mRNA itself causes the allergic
reactions."
In
addition, the data suggest that reactions to the COVID-19 vaccines were
generally not the most severe form of allergic reaction, which is good news in
terms of vaccine safety, she said. Allergic reactions mediated by IgG and
basophils can be managed with antihistamines, fluids, corticosteroids and close
observation, meaning that many individuals who have had a reaction to their
first vaccine dose can safely receive a second dose under medical supervision.
PEG is widely used as a stabilizer in household products, cosmetics and medications, with women more likely to be exposed to large quantities of the substance, possibly explaining why more vaccine allergies have been seen among women. (Repeated exposures to a substance can sometimes sensitize the immune system and provoke allergies.)
Because most reactions were to PEG rather than
the vaccine's active ingredients, it is likely that vaccine manufacturers can
reformulate the vaccines with different stabilizers that are less likely to
cause allergies, Nadeau said.
The research was supported by the Asthma and Allergic Diseases Cooperative Research Centers (grant U19AI104209), the National Institutes of Health (grant R01AI140134), the National Institute of Allergy and Infectious Disease SARS Vaccine study (grant UM1AI10956508), the Parker Foundation, the Crown Foundation and the Sunshine Foundation.
