Covid-19 vaccines for children under 5 may be approved by the US Food and Drug Administration (FDA) next month and become available in the US soon after.
The first covid-19 vaccines for people aged 16 and older were approved by authorities in the UK and US in early December 2020, and within days, shots were going into arms. This all took place less than a year after the virus was identified – the fastest vaccine development in history.
FDA approvals for younger age groups then came in five-month increments: first for 12 to 15-year-olds in May 2021 and then for 5 to 11-year-olds in late October of the same year. In other countries, there were similar roll-outs.
Yet more than two years into the pandemic, most children under 5 are still waiting for their chance at a jab, leaving many parents frustrated by what feels like a delay. Only seven countries – Argentina, Bahrain, China, Chile, Cuba, Hong Kong and Venezuela – have approved a vaccine for younger children, mostly those 3 years or older. Cuba and Venezuela are the only countries where children as young as 2 can currently get vaccinated. That may soon change.
On 28 April, Moderna requested an emergency use authorisation (EUA) with the FDA for its covid-19 vaccine for children under 6. The next day, the company filed a request for authorisation with European Union authorities and says similar requests are now under way with other international authorities.
In February, Pfizer/BioNTech paused an EUA request for its covid-19 vaccine in children under 5 after preliminary data revealed a two-dose regimen was less effective. It plans to submit data for a three-dose regimen by late May or early June, according to a company spokesperson.
The FDA plans to convene in June to review data for both vaccines, and if all goes well, one or more could become available that month, Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, told The Washington Post. Similar approvals would probably follow elsewhere in the world.
Why are children under 5 the only age group without a covid-19 vaccine?
It is normal for very young children to be the last age group targeted in vaccine development. All vaccines, even those intended for use in children, must be tested and proven safe and effective in adults before trials in children, says Lorry Rubin at the Cohen Children’s Medical Center in New York. Researchers then work down through younger age groups: 12 to 17-year-olds, then 5 to 11-year-olds and finally children under 5, says Rubin.
Beyond ensuring vaccine safety, this approach helps developers determine dosing. Once an adult dose is established, they can use this information to find a comparable dosage for children, says Robert Frenck at the Cincinnati Children’s Hospital Medical Center in Ohio.
How is vaccine dosing different for kids?
Vaccine doses are determined by what are known as dose-ranging studies: a small number of participants – usually between a few dozen and a few hundred – receive either a placebo or a low, middle or high dose.
For adults, the initial range of doses is based on animal studies. Once an efficient and safe dose is determined, it is then tested against a placebo in much larger trials, usually with tens of thousands of volunteers. This is a time-consuming process as researchers must wait until a certain percentage of the control group becomes infected before they can calculate vaccine efficacy, says Frenck.
With children, vaccine manufacturers can skip this final, lengthy step. Instead of comparing against control groups, they compare whether antibody levels in vaccinated volunteers get to the same levels shown to provide protection in adults or older groups of children.
“If we can get to that same antibody level in a younger population then the FDA will accept that as a proxy, for this is likely to result in [the same level of] protection,” says Rubin.
Dose-ranging studies must still be conducted for children, but instead of basing doses on animal studies, developers use data from the age group above, says Frenck. For example, based on a 100-microgram dose producing a sufficient immune response in those 12 and older, Moderna tested three different doses in children aged 6 to 11: 100, 50 and 25 micrograms. It found 50 micrograms induced an immune response comparable to that in adults.
“I don’t think it was done too quickly, but I don’t think we could have done it much faster”
Pfizer/BioNTech found that one-third the effective adult dose produced the same number of antibodies for children aged 5 to 11.
Once a dose is pinpointed, the last step before submission for approval is to test it in a few thousand kids to see if it triggers an adequate antibody response. Not having to wait until a big enough portion of the placebo group has been infected makes vaccine development in children quicker – it took nine months to develop a vaccine for adults versus six months for 5 to 11- year-olds – but it still takes time.
“We are moving along at a reasonable pace, and I don’t think any corners were cut,” says Frenck. “I don’t think it was done too quickly, but I don’t think we could have done it much faster.”
What do we know about the vaccines for kids under 5?
Moderna’s vaccine for children under 6 requires two 25 microgram doses – or one-quarter their adult dosage, according to a press release from the company. The vaccine was 43.7 per cent effective at preventing infection in those aged 6 months to under 2 years old and 37.5 per cent effective at preventing infection in those aged 2 to under 6 years old. There were no cases of severe disease, hospitalisation or death in either the vaccinated or control groups.
When specifically tested against omicron, Moderna’s vaccine is 44 per cent effective at preventing infection in adults – comparable to its effectiveness in children.
Pfizer/BioNTech’s vaccine for children uses three 3 microgram doses – or one-tenth the adult dose. Frenck notes that you can’t directly compare this dose against Moderna’s since the formulations of the two vaccines are different.
Last December, Pfizer/BioNTech announced it would add a third dose to the vaccine regimen for children aged 5 and under after preliminary results found two doses didn’t produce enough antibodies. According to a spokesperson for Pfizer, the third dose increases immune response while minimising potential side effects. The company hasn’t yet released data on the efficacy of the three-dose series in preventing infection or hospitalisation. Pfizer declined to comment on why it chose to add an extra dose rather than increase the dosage of its two-shot series.
“I obviously cannot speak for a clinical decision made by Pfizer, but you have one of two choices. Either increase the dose, which potentially translates to more side effects, or give another low dose,” says Frenck. “That’s my guess for why Pfizer decided to use three doses. It [probably] gives a better safety profile.”
How long will it take the FDA to approve the vaccines?
The FDA has set tentative dates in June to assess Moderna’s EUA request for its covid-19 vaccine in children under 6. Marks said that if Moderna and Pfizer/BioNTech complete data submission within one week of each other, he would consider presenting the vaccines on successive days. The FDA is still awaiting final submissions from Moderna.
“While the FDA cannot predict how long its evaluation of the data and information will take, we will review any EUA request we receive as quickly as possible using a science-based approach,” says Abigail Capobianco, a press officer for the FDA.
In an interview with The Washington Post, Marks said approval may take a few weeks longer than past emergency authorisations. That is because vaccine-induced fevers in young children can be more serious than in adults. The extra time will allow them to weigh the risk of potential febrile seizures against the benefits of vaccination.
How is vaccine safety tested for children?
Safety is assessed at each stage of vaccine development. One of the benefits of starting in adults and working down through age groups is that by the time a vaccine reaches children under 5, manufacturers have an even better grasp of potential side effects and can monitor them more closely.
For instance, once it became clear that myocarditis – a condition characterised by dangerous yet treatable heart inflammation – was a potential risk of covid-19 vaccines, developers increased the number of children enrolled in vaccine trials, says Rubin. This allowed them to better assess the risk of the condition, which is actually more common after covid-19 infection than vaccination.
So far, trials in young children indicate that side effects of covid-19 vaccination for this age group are the same as those in adults, including things like swelling at the injection site and headaches, says Frenck. The only difference is that there is no apparent risk of myocarditis, probably due to smaller vaccine doses.
“We know the risk of myocarditis in vaccinated children between 5 and 11 is one-tenth of what it was in the 12 and above age groups,” says Frenck. “So, it’s basically non-existent, it’s the background rate, and I would assume the same is true for 5 and under.”
Should young children still be vaccinated even if they have already had covid-19?
The US Centers for Disease Control and Prevention (CDC) estimates that more than 75 per cent of children aged 11 and under have already had covid-19, which has led many parents to question the need to vaccinate their children.
According to a poll conducted earlier this month by the Kaiser Family Foundation, about 18 per cent of parents with children under 5 say they plan on vaccinating their child as soon as possible, while 27 per cent say they will “definitely not”. Most parents fall somewhere in the middle, with 38 per cent saying they plan to see how the vaccine works in others and 11 per cent saying they will only vaccinate their kids if it is required.
Rubin says the extra precautions taken by the FDA and vaccine manufacturers as part of the approvals process are likely to reassure parents of the vaccine’s safety and efficacy.
He says that even children who have already been exposed to covid-19 will benefit from vaccination as it will further boost their immunity and reduce the risk of reinfection.
Unvaccinated adults with a previous covid-19 infection are twice as likely to become re-infected than vaccinated individuals with no history of infection, probably because natural immunity is short-lived compared with vaccine-induced immunity, says Rubin. The same is probably true of children as well.
Preventing re-infection is important not only because it reduces the chances of developing covid-19 complications, including those associated with long covid, but it also reduces transmission to others. Plus, it will help keep kids in school and other activities that are important for their development, says Frenck.
Even if a child is in good health, vaccination is still important: 63 per cent of infants and children hospitalised with covid-19 between December 2021 and February 2022 had no underlying health conditions, according to a report from the CDC.
“My goal is to keep kids out of the hospital, to keep them out of the ICU, to keep them from dying,” says Frenck. “I have to assume every child is at risk for having severe disease, and that’s why you want to vaccinate everyone.”
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