By Rachel Levene, PhD Candidate in Molecular Microbiology at Tufts University School of Medicine and daughter of Dr. Eric Levene, Chester Pediatrics.
The FDA is expected to announce early next week that Pfizer-BioNTech’s COVID-19 vaccine will be granted emergency use authorization (EUA) for adolescents aged 12-15 years (it already has EUA for those 16+). This is incredible news and I am incredibly excited that 12-15-year-olds will be able to be protected from COVID-19. Even though children are at less risk for severe disease from the virus that causes COVID-19 (SARS-CoV-2), they can still spread the virus to other children and adults. Since there is emerging data that the mRNA vaccines (Pfizer-BioNTech and Moderna) prevent asymptomatic infection and likely transmission, vaccinating children will significantly lessen the likelihood that they could carry the virus and transmit it to others. Vaccinating a high percentage of the population is expected to drastically reduce the amount of virus circulating and help us to return our pre-pandemic lives including children in school for 5 full days, their after-school activities, and being with friends and family!
How do we know the vaccine is safe and effective in children aged 12-15?
Pfizer-BioNTech performed a clinical trial testing the same vaccine given to adults in adolescents aged 12-15, much like they did for adults. They enrolled about 2000 adolescents aged 12-15 and randomized them to receive either the vaccine (same dose given to adults) or a placebo. Adolescents were then followed to see if they developed COVID-19 and had their antibody levels measured. Much like the adult trials, a certain number of cases of COVID-19 and how those cases are spread between the placebo and vaccine are used to estimate vaccine efficacy. After a period of time, the placebo group had 18 cases of COVID-19 and the vaccine group had none! This is where the 100% efficacy comes from. While it’s unlikely that the vaccine efficacy will be exactly 100% in the “real world,” we know from real-life studies in adults that the vaccine efficacies in the trials are pretty close to what will happen in the real world. Additionally, participants’ antibody levels and other immune markers were measured and they had similar antibody levels and immune markers to that of young adults in the original adult trial. Since having these antibodies and immune markers is likely protective against COVID-19 and they are similar to adults, researchers can also “bridge” the vaccine efficacy results from adults to children: this is called immuno-bridging.
It was reported that many of the adolescents in the trial had side effects similar to that of young adults like headache, fatigue, sore arm, low-grade fever, etc. Importantly, they are short-lived and tend to dissipate within 48 hours after receiving the vaccine. These side effects mean the immune system is doing its job! However, if you or your child do not have side effects it does not mean your immune system is not working; there were people in the trials that didn’t have side effects – everyone is different!
The FDA reviewed all the efficacy and safety data and their likely decision to grant EUA reflects that they feel that the vaccine is safe and effective and the benefits outweigh any risk. Federal, state, and local agencies are working to make sure that adolescents can receive the Pfizer-BioNTech vaccine soon after authorization.
Moderna is currently conducting a clinical trial of their vaccine in 12-17-year-olds using the same adult dosage. They expect results very soon. Since Pfizer-BioNTech’s and Moderna’s vaccines are based on the same platform (mRNA), it is very likely that Moderna will soon be able to share good news!
What about children younger than 12 years old?
Clinical trials in children under 12 years old have recently started. These trials are a bit more involved and complicated than the adolescent trials. Young children tend to have very robust immune systems and they may not need the same dose as adults and adolescents to elicit a protective response. In fact, it is possible that the adult dose could be too high for them. Hence, one of the purposes of this trial to figure out a dose that is both safe and effective for young children. This is very similar to the adult Phase I trials – researchers started with different doses before deciding which was safe and most likely to be effective. Safety is of the highest concern for these trials.
Determining the dosage is done via age-de-escalation and dose-escalation. This means that investigators start with the oldest children (9-12) before moving down to younger children (6-9) and younger children (2-6 and 6months-2years). Additionally, they start with the lowest dose and then increase the dose once they are sure that there were no serious side effects with the lower dose. These trials have multiple groups of children in each age group that receive different doses. After a period of time, blood is drawn from the participants, and antibodies and immune markers are measured. The levels of antibodies and immune markers are compared to those of young adults and “immuno-bridged” to see which dose gave might give an effective immune response, i.e. which was most similar to young adults and adolescents. The lowest dose that elicits an effective immune response and that is well-tolerated (i.e. fewest side effects, etc) is usually chosen to move forward to larger efficacy trials. The dose chosen may be different for each age group (9y-12y, 6y-9y, 2y-6y, 6m-2y). Once a dose is determined, more children in each age group are enrolled (~4000-6000 children total) and randomized to receive either the vaccine at the previously determined dose or a placebo. Like the adult trials, they are then monitored to see if they develop COVID and they have their antibody levels and immune markers measured. After a certain number of cases (determined by statistical modeling) and how the cases are spread between the vaccine and placebo group, efficacy is calculated.
Both Pfizer and Moderna have started these age-de-escalation and dose-escalation trials in children under 12 and are currently at the phase of determining the dose for each age group. Pfizer announced that they expect to have results by September 2021. They will then submit a request for EUA to the FDA and all data will be rigorously evaluated by a committee of experts.
If you have questions about the vaccine, contact your Trusted Allied Pediatrician.
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