Effective vaccines designed to protect against SARS-CoV-2, the virus that causes COVID-19, have received emergency use authorization from the FDA and are now being distributed to patients across the United States. These vaccines are considered the most important development to date in the battle against the pandemic.
The mechanism of action of the new vaccines, as well as safety and efficacy issues, were explored by John M. Kelso, MD, Division of Allergy, Asthma & Immunology, Scripps Clinic, San Diego, CA, and Clinical Professor of Pediatrics and Internal Medicine, University of California San Diego, during a recent podcast hosted by the American Academy of Allergy, Asthma & Immunology (AAAAI).
Dr Kelso began his discussion by noting that evidence and recommendations regarding these newly approved vaccines continues to evolve and are therefore subject to change.
“Two vaccines are currently approved by the FDA, which allows us to have some hope and see the light at the end of the tunnel. The vaccines have come not a moment too soon, with horrific numbers of deaths and cases each day. I am hopeful that this will bring us to the other side of the pandemic,” he said.
According to Dr Kelso, most vaccines include a small amount of a modified form of the infectious agent, which allows the body to mount an immune response that does not cause the disease itself; this immune response is protective when a person is exposed to the actual virus or bacteria.
“Vaccines are one of the most important and successful achievements of modern medicine,” Dr Kelso said. “These include vaccines for measles, mumps, pertussis, polio, and Hemophilus influenza type B.”
The Moderna and Pfizer/BioNTech vaccines both use messenger RNA (mRNA) technology, which differs from the technology used for other approved vaccines. A tiny piece of this genetic material encodes for the spike proteins that give the COVID-19 virus access to cells. Once the vaccine is injected, the cells in the body take up mRNA and start producing the spike protein, stimulating a robust immune response that includes production of antibodies and lymphocytes to combat the infection, Dr Kelso explained.
“The spike protein itself cannot cause infection, but antibodies against it will work against the virus by attaching to the spike protein on the virus. Neither the mRNA or the spike protein in the vaccine can cause infection, and neither persists permanently in the body,” he said.
Dr Kelso emphasized that although the process for developing the 2 vaccines and approving their use occurred at record speed, the safety data are reassuring.
“Other than the fact that the timeline for developing the vaccines has been condensed, the review process and the studies have been sound. People can have confidence that these vaccines are safe and effective,” he noted. “The process has been transparent. All the safety and efficacy data are available, and no shortcuts were taken. I hope that inspires confidence.”
Studies of the vaccine met the gold standard. These were large, well-designed, randomized, placebo-controlled clinical trials that enrolled more than 70,000 participants in total. Participants in both trials received 2 doses of the vaccine or placebo and were followed over time. Once each study was completed and the results unblinded, the vaccines were found to be highly effective, reducing the risk for developing COVID-19 by approximately 95%. In addition, none of the vaccine recipients in the trials developed severe disease, indicating that, even for those few patients who developed COVID-19 despite of receiving the vaccine, the vaccine offered some protection.
Thus far, there is no evidence that the vaccines are interchangeable, so the recommendation is for patients to receive the same vaccine for 2 doses.
Common side effects associated with the vaccines include local reactions at the site of injection—redness, pain, heat, and soreness. In addition, as with any vaccine, there can be systemic adverse effects for 1 or 2 days, such as headache or fatigue.
“These symptoms indicate that your body is mounting an immune response,” Dr Kelso said.
In the clinical trials, the only exclusion related to allergies was a previous allergic reaction to another vaccine, which is uncommon.
“There were no serious reactions, and nobody developed anaphylaxis,” Dr Kelso said.
At the time of the podcast, the vaccine had been out in the community for 2 weeks, and there were isolated reports of allergic reactions. As of late December 2020, 6 anaphylactic reactions had been reported among 300,000 people who received the vaccine, and all resolved with epinephrine.
“This represents a tiny percentage, but anaphylaxis is a potentially serious reaction that can occur with all vaccines. With other vaccines, about 1 in 1 million people will have anaphylaxis, so it is not surprising that it did not occur during the clinical trials of the vaccines,” Dr Kelso noted.
“We only have vague details thus far regarding anaphylactic reactions, but they occurred within minutes of the injection. Most allergens are proteins, and COVID-19 vaccines do not contain proteins. Polyethylene glycol [PEG], which has not been previously used in vaccines, is used in the mRNA COVID-19 vaccines. PEG is currently the focus of inquiry regarding anaphylaxis with the vaccines, but it is still very early, and we will need to study this further,” Dr Kelso said. “It could be due to another mechanism, but it is not sorted out at the moment.”
“It will be important to identify any potential culprit allergen, which will include using the vaccine for skin testing on patients who may have suffered these reactions as well as control subjects. This need not require wasting precious doses of the vaccine because residual vaccine from the multidose vials can be used for this purpose. A small number of laboratories have assays for serum-specific antibodies to PEG, and this is being studied,” he explained.
Dr Kelso advised that providers obtain a blood sample from patients who have an apparent anaphylactic reaction to the vaccine to test for serum tryptase level. “If the level is elevated, it confirms the diagnosis of anaphylaxis, but if it is not elevated, the test does not necessarily exclude the diagnosis.”
Patients with a history of allergic reactions or anaphylaxis should be monitored for 30 minutes after receiving the vaccine, and all patients should be monitored for 15 minutes. Any serious allergic reaction would almost certainly begin within this time frame and could be promptly and effectively treated with epinephrine.
Nonallergic reactions to the vaccine may also occur. For example, a vasovagal reaction can mimic an allergic reaction. Both anaphylaxis and a vasovagal reaction can result in lightheadedness or syncope, but in anaphylaxis this is usually preceded by flushing and a reflex tachycardia, whereas in a vasovagal reaction this is usually preceded by bradycardia and pallor.
“Vasovagal reactions have been reported with other vaccines,” Dr Kelso said.
Other nonallergic reactions to the vaccine may include anxiety attacks that cause respiratory distress and mimic anaphylaxis.
As experience with the COVID-19 vaccines expands, reactions will be reported through the vaccine adverse event reporting system. The Centers for Disease Control and Prevention also has a smartphone app that can be used to report reactions in real time.
“We have active ongoing monitoring for safety signals,” Dr Kelso said.
Protective immunity begins to develop after the first dose of the vaccine, and full immunity occurs within 1 week to 10 days of the second dose.
After being vaccinated, people should continue to wear masks and social distance, because the pandemic will still be ongoing. “Until there is evidence of herd immunity in approximately 60% to 80%, these measures are needed,” Dr Kelso said.
“A person who is vaccinated is not completely protected and could still spread the disease. The likelihood is small, but while the disease is still rampant in the community, everyone who is vaccinated needs to take those measures. If you have had COVID-19, you should still get the vaccine. No one knows how long protection from the vaccine will last. It is possible, although quite rare, to have the disease more than once,” he noted.
“Pregnancy and breastfeeding are not contraindications for receiving the vaccine. We do not have long-term safety data yet, but there is no reason to believe that the vaccine poses any risks to pregnant women or those who are breastfeeding, particularly given the seriousness of the disease we are trying to prevent,” Dr Kelso explained.
“As we go along, we will learn more. For the moment, these vaccines that are safe and effective will turn the tide. I am absolutely going to get the vaccine. It took me half a second to press the button to say yes. I am jealous of my colleagues who have already received it. ‘Vaccine envy’ is going around,” he said.
To listen to the entire podcast on the AAAAI website, please go to http://enews.aaaai.org/podcast/episode-42.mp3.