USF Health has been selected to perform an eight-to-10-week clinical trial to investigate allergic reactions to COVID-19 vaccines to increase public trust and development of future mRNA vaccines.

Founded by the National Institutes of Health (NIH), the study will use research from USF’s trials and up to 34 other allergy-research centers in the U.S. to determine whether people considered high risk for allergic reactions or mast cell disorders will react negatively to COVID-19 vaccines.

Before the Pfizer-BioNTech and Moderna vaccines were deployed in the U.S., two cases of anaphylaxis occurred in the U.K. As both vaccines are distributed across the U.S., the primary goal of the trial is to understand why these reactions are occurring and increase public trust toward mRNA vaccines and fine-tune future vaccines to prevent such reactions.

Lisa Wheatley of the NIH reached out to Thomas Casale, professor of medicine and pediatrics in the division of allergy and immunology at USF Health and chief medical advisor of the nonprofit Food Allergy Research and Education, to be an investigator in the trial due to his expertise and experience with other NIH trials in the past.

“What’s been found is that the incidence of having these acute allergic reactions is higher with the Pfizer and Moderna vaccines than with typical vaccines,” said Casale. “[Pfizer-BioNTech] is about 10 to 12 and a half per million doses, so it’s not like it’s real common, but a typical vaccine is only about one in a million. Moderna is less than about two and half per million.

“When patients who had these reactions were looked at, there were a couple things that stood out. The majority were female, and most of the patients had a history of bad allergic diseases.”

In response to these findings, the NIH and National Institute of Allergy and Infectious Diseases designed the clinical trial with the purpose of enrolling two types of patients. Two-thirds of the patients enrolled must be considered high risk with a history of acute allergic disorders, such as food, insect or drug allergies, while the other one-third must have no history of allergies to act as a control group. 

So far, nine patients have been vaccinated and Casale hopes to enroll 120 total participants. Because of the double-blind method implemented in the study, Casale isn’t currently aware of who has received a vaccine or a placebo. Nationwide, over 3,000 people are expected to participate in the clinical trials.  

“We still don’t know what it is that’s triggering these allergic reactions,” said Casale. “We know it’s not the mRNA because mRNA is not going to give you an allergic reaction. It’s most likely what we call an excipient, put in vaccines to prevent it from breaking down or becoming contaminated. We think it’s that, but we don’t know for sure, so that’s the purpose of doing this trial.”

The trial was delayed several months due to the NIH’s inability to secure both vaccines, and it just started Monday. However, the researchers have also experienced difficulties in finding people to sign up for the trial due to the vaccine now being widely available. Participants are selected through an online interview to determine if they are a good candidate for the trial.

All participants will be compensated $75 for each visit to the clinical research unit on Bruce B. Downs Boulevard. 

Patients will be notified within a couple days of when they can receive their second dose of their respective vaccine within three to four weeks’ time, or, if they received the placebo, their first dose.

Casale said that the age range for participants was 18 to 69, though with the recent protocol amendment, it might drop to 16.

“[Participants] must be relatively healthy, because if you had an acute allergic reaction, we don’t want to put you at risk if you have underlying conditions such as coronary artery disease. It might make it harder for us to treat and reverse the reaction. Certain medications are also exclusionary,” said Casale.

Both participants and researchers are blinded by a doctor of pharmacology in a double-blind method to ensure both parties are unaware of who gets the active vaccine or the placebo. Blood and genetic samples are taken before and after the vaccine is given, and then patients are put under observation for an hour and a half to make sure no adverse effects occur. 

After the participant has been fully vaccinated, the long-term observation starts.

“We have to keep track of the patients for 30 days afterwards. If there is an adverse untoward event, we need to know about that so we can report it to the FDA,” said Casale.

“As we’re doing the study, the data gets entered into a computer and that all goes to a central repository. When the study is done, the data are examined quickly and if there’s any unanswered questions, they’re answered, and then they’re analyzed to determine what the results were.”

If patients who received the vaccine have an adverse reaction, they have to report it to the clinic or physician that gave them the vaccine to track and learn what reaction occurred and the cause of it in order to prevent it in the future. 

The information provided will go toward understanding components of current and future mRNA vaccines to find out how to lessen allergic reactions and better treat those who experience them, according to Casale.

“Finding out the cause of a patient’s allergic reactions, whether it’s a patient’s characteristics or genetic predisposition or underlying disorders, would be very important to understand,” said Casale. 

“If we can show that the [mRNA] vaccines are relatively safe and effective as other vaccines, then hopefully more people will be eager to get them. Not only for [COVID-19], but for whatever pandemic we might face in the future.”