The pandemic has many parents asking two burning questions. First, when can I get a vaccine? Second, when can my kids get it? It may surprise you that the answers are not the same. Adults may be able to get a vaccine by next summer. But their children have to wait longer. Maybe much longer.
Thanks to Operation Warp Speed and other U.S. government programs, a number of adult Covid-19 vaccines are already in advanced clinical trials. However, studies have not yet begun in the United States to determine whether these vaccines are safe and effective for children.
On Friday, Dr. Anderson and colleagues made a comment in Clinical Infectious Diseases magazine urging vaccine manufacturers to band together. They called it “Warp Speed for Covid-19 Vaccines: Why Are Children Stuck in Neutrality?”
The search for a Covid-19 vaccine began as soon as the researchers isolated the virus in January. Development teams around the world began developing vaccines based on various techniques. For example, some used inactivated coronaviruses, which stimulate the immune system to make its own antibodies. others delivered viral genes into the body and triggered immune cells.
When they were ready to test these vaccines, they went down a well-worn trail of stringent protocols that had been developed over decades to determine if a vaccine was safe and effective. Vaccines require particularly rigorous testing because they are fundamentally different from drugs, which are intended for a limited number of people with a specific disease. On the other hand, millions of healthy people are being treated with vaccines to keep them from getting sick in the first place.
After testing a vaccine on animals, developers begin clinical trials in humans. These trials take place in three phases, from small to large. Phase 1 and 2 trials can help vaccine developers determine which dose is likely to be safest while providing the best immune protection.
Phase 3 trials, the final phase of vaccine testing, are conducted on thousands or tens of thousands of volunteers. During these studies, scientists can obtain clear evidence that a vaccine protects people from disease. They can also reveal side effects that were missed in smaller studies.
Many vaccines – including against measles, polio, and tetanus – were developed for children from the start. In such cases, vaccine developers usually begin studies in adults to see if there are significant safety issues.
Only if the researchers found no serious side effects would they test them in children, often starting with teenagers and then working their way through to younger ages. Vaccine developers are well aware that children are not just miniature adults. Their biology differs in ways that can affect how vaccines work. For example, because their airways are smaller, they can be prone to low rates of inflammation, which can be harmless to an adult.
These studies allow vaccine developers to adjust the dose to get the best immune protection with the least risk of side effects. The doses adults and children need are sometimes different – for example, children receive smaller doses of hepatitis B vaccines, but larger doses for pertussis.
This process has proven to be safe and extremely successful. In the past few decades, vaccines for children have saved millions of lives. Just expanding access to measles vaccine resulted in a 78 percent decrease in mortality between 2000 and 2008 and prevented an estimated 12.7 million deaths worldwide.
In the past, the tests required for a vaccine to be approved by the Food and Drug Administration may have taken a decade or more. Over the past few years, researchers have shown ways to accelerate their development without sacrificing the research necessary to show they are safe and effective.
When the Covid-19 pandemic hit, some vaccine manufacturers figured out how stages could be combined to collect more data over the same time period. Governments and philanthropic organizations offered support for expensive clinical trials and for the construction of factories to manufacture vaccines that had not yet proven themselves.
The result was an unprecedented and rapid march towards a vaccine. Just nine months into the pandemic, at least 38 Covid-19 vaccines have reached clinical trials, and dozens more are set to begin in the coming months.
By the summer, the earliest vaccines showed promising results for clinical trials. The vaccines caused no serious side effects in the volunteers and produced promising levels of antibodies. At that point they moved into phase 3 studies.
Dr. Anderson said vaccine manufacturers could have started running studies in children this summer once they got good Phase 2 results from adults. But that didn’t happen. And that still hasn’t happened with autumn around the corner.
Whenever these studies begin, it can take over a year to get vaccines for Covid-19 for children. Vaccine manufacturers must write protocols and get FDA approval. You have to recruit volunteers – a process that is more time consuming for pediatric vaccines as parents have to provide informed consent. It may take a few months to reach the first injections.
Necessarily, the studies would have to start small, with researchers perhaps giving only half a dozen children a low dose of the vaccine and then monitoring them for several days. Then the process could expand to dozens and then hundreds of children.
It could be a few more months while the vaccine developers give a small group of children a low dose. Each group of children would need two months of observation to check their immune responses and make sure they were not experiencing any side effects. Only then would vaccine developers start a new study with a higher dose.
These tests would likely begin with older children before researchers could switch to children between the ages of 3 and 8. And only after collecting early data from this study would it be possible to start one for children under 3 years of age. Once all the results of these studies are in, when the FDA approved the vaccines for children, it needed an independent review.
There were good reasons for the early focus on adults. Children die much less often from Covid-19. On Friday, the Centers for Disease Control and Prevention published a report that found that of the more than 190,000 people who died with Covid-19 in the United States, only 121 were under the age of 21. Likewise, the hospitalization rate for children under 18 is 20 times lower than for adults.
“Currently, children are not a risk group,” said Dr. Paul Offit, professor at the University of Pennsylvania and a member of the FDA’s Vaccine Advisory Board who was not involved in the new comment. “Given the limited time and resources for these studies, I can understand why the initial focus is on people over the age of 18.”
Dr. Offit believed that a reasonable time to start trials on children could be after the first batch of approved vaccines for healthcare workers and other high-risk groups is launched – possibly in early 2021.
Dr. Kristin Oliver, pediatrician and vaccine specialist at the Icahn School of Medicine on Mount Sinai, also believed that trials for children should wait – at least until one or more vaccines successfully pass phase 3 trials. “We don’t know who will make it,” she said. “I am very excited to have a safe and effective vaccine, but I keep my excitement at bay.”
But Dr. Anderson and his colleagues don’t want to wait that long. In their comment, they said phase 2 studies in children “should start now”.
They argued that even if a few hundred children die from Covid-19, those are deaths that could have been avoided with a vaccine. In addition, doctors are learning a lot about the effects of this new virus on children. In May, they discovered that an entirely new disease could develop called Multisystem Inflammatory Syndrome in Children, or MIS-C for short. Further long-term effects of the virus on children remain to be seen.
AstraZeneca, Johnson & Johnson, Moderna, and Pfizer all said they would focus on developing a vaccine for children.
“Moderna agrees with the importance and urgency of pediatric clinical trials for vaccines against Covid-19,” said Ray Jordan, a company spokesman, in an email. “We plan to begin pediatric trials in the near future, subject to regulatory approval.”
Amy Rose, a Pfizer spokeswoman, said the company is “actively working with regulators on a potential pediatric study plan to address the burden of disease in pediatric populations under the age of 16”.
Dr. Anderson viewed these statements as little more than vague promises and a substitute for real steps toward a pediatric vaccine. “In the meantime, we are neutral about ongoing child deaths and illnesses,” he said.
In addition to protecting children’s health, Dr. Anderson and his colleagues, a Covid-19 vaccine, which could be ready by the beginning of the 2021 school year, could slow down the transmission of the virus between students, their parents and school staff. Vaccinating children could help reopen society and ensure schools don’t become hot spots for widespread events.
“You are absolutely right,” said Dr. Grace Lee, associate chief physician for practice innovation at Stanford Children’s Health and professor of pediatrics at Stanford University School of Medicine. “So that we can effectively reopen, we need vaccines for children.”