The University of Oxford’s Jenner Institute and Oxford Vaccine Group in the United Kingdom has announced that its researchers have begun recruiting children aged five to 12 years for phase II and phase III clinical trials testing an experimental COVID-19 vaccine the university is developing in partnership with AstraZeneca plc.1
Oxford’s ChAdOx1 nCov-19 (“chimpanzee adenovirus Oxford 1” novel coronavirus-19) recombinant vaccine is made from a genetically modified adenovirus that infects chimpanzees used as a viral vector into which the COVID-19 genome is inserted so the cells of the human body express the new coronavirus’s Spike Protein (S) and induce antibodies that are supposed to prevent infection.2Some researchers have noted that, “Viral vector-based vaccines require assessment of efficacy and safety, including immunogenicity, genetic stability, ability to evade pre-existing immunity, replication deficiency or attenuation, and genotoxicity.”3 Others have emphasized that the selection of an appropriate viral vector for a new vaccine depends upon “a thorough knowledge of the infectious agent for which the viral-vectored vaccine is being developed.”4
There are gaps in scientific knowledge about the origin of the new coronavirus and the biological mechanisms involved in the way it infects and causes disease in humans but, like most COVID-19 vaccines being fast tracked to licensure, the vaccine being created by Oxford/AstraZeneca is compressing clinical trials testing into months rather than years.
Phase I, II, III Clinical Trials Of Oxford COVID-19 Vaccine Held Simultaneously
The phase I trial began in April when over 1,000 healthy adult volunteers received their experimental “ChAdOx1 nCoV-19” vaccine. Phase II expanded the age range to include those aged five to 12 years, 56 to 69 years, and those over age 70 to assess the immune response to the vaccine in people of different ages and find out if the immune system responses of older people and children are different. The phase III part of the study assesses how the vaccine works in a larger number of people over age 18 in terms of preventing infection and symptoms of COVID-19.
In the U.K., recruitment of children to participate in vaccine trials is usually done through doctors’ offices and by health care workers. The experimental vaccine being tested in clinical trials is often given at home and parents are asked to take regular temperature readings and a diary of their child’s reaction, with follow-up visits and blood tests.5 There is no financial incentive to join the vaccine trial, and parents can withdraw their child at any point. The clinical trial team also gives the child participant other routine vaccinations during home visits for the length of the study.6
Vaccine Trials Don’t Pick Up All Side Effects
Personal benefit and contributing to “the greater good” are the two most common reasons parents cite for enrolling their children in vaccine trials, according to Shamez Ladhani, MRCPCH, PhD, a pediatric infectious disease consultant at St. George’s Hospital in London, and consultant epidemiologist for Public Health England. He commented that, while there are risks, vaccine adverse reactions are rare—so much so that they often don’t get noticed until the vaccine goes on sale and is given to many more patients.
Dr. Ladhani, who is frequently involved in vaccine trials, said:
Some side effects you actually don’t find out until you have given 100,000 doses—that’s always a worry—but there isn’t a clinical trial that’s big enough that can pick that up.7
Children appear to be less affected by COVID-19, although their role in transmission of the virus remains unclear. In the U.S., 1.7 percent of COVID-19 cases for which age was known occurred in children younger than 18 years, even though they make up 22 percent of the U.S. population.8Additionally, relatively few children with COVID-19 are hospitalized, and fewer children than adults experience fever, cough, or shortness of breath.
Children May or May Not Be Last to Get COVID-19 Vaccine
As scientists race to develop a COVID-19 vaccine, some are acknowledging that children could be among the last to be vaccinated.9 The process for testing a COVID-19 vaccine in children could take “extra months and maybe years longer,” according to Paul Duprex, PhD, Director of the Center for Vaccine Research and professor of microbiology and molecular genetics at the University of Pittsburgh.
However, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID) and a member of the White House Coronavirus Task Force, commented that it’s possible that studies in children might “catch up” to those in adults, if they are done correctly. “There is no reason not to believe that [a vaccine] wouldn’t be available simultaneously for adults and children,” Dr. Fauci said.10
Duke University Professor Sallie Permar, MD, believes children are “key” to ending the COVID-19 pandemic and testing vaccines in children must be a priority because, “If we prioritize children now in the steps we take to end this pandemic, we will protect them while protecting all members of our community.” In USA Today, she recently advocated for experimental coronavirus vaccines to be tested in children once safety testing in adults is completed:11
Early trials of coronavirus vaccine safety and immune responses have excluded children. Once safety testing is completed in adult volunteers, however, leading candidate vaccines should be tested for safety and effectiveness in children. And once safety and efficacy are established, children should be among the first to receive the vaccine.
Throughout history, scientists have consistently found that infants and children are not simply small adults. Children’s bodies and maturing immune systems function differently from adults,12which is why pharmaceutical products are often studied separately in children and adults. Already, scientists are pointing out differences in immune system responses by children to COVID-19 infections compared to responses by adults, who are at increased risk for complications.13
Oxford’s COVID-19 Animal Trials Failed But Manufacturing Ramps Up
The University of Oxford and AstraZeneca researchers are proceeding with testing the experimental ChAdOx1 nCov-19 vaccine in children, even though a May 13, 2020 published report indicated that small trials of the vaccine in mice and monkeys were not successful in proving effectiveness against infection. Although the animal trials provided evidence that the experimental vaccine induced a “robust humoral and cell mediated response” in mice and appeared to protect against development of viral pneumonia in monkeys, it did not prevent infection with COVID-19.1415
On June 5, 2020, Market Watch reported that AstraZeneca has begun manufacturing two billion doses of Oxford’s COVID-19 vaccine before clinical trials have been completed and results analyzed and published, reportedly in August. AstraZeneca has received more than $1B in funding from the U.S. government to accelerate development of its vaccine and deliver 300 million doses to the U.S., which will include a Phase 3 clinical trial in the U.S. this summer involving 30,000 volunteer participants.16
According to Market Watch:
AstraZeneca has struck a $750 million agreement with two health organizationsbacked by [Bill] Gates and his wife Melinda—the Coalition for Epidemic Preparedness Innovations and Gavi, the vaccine alliance—to provide and distribute 300 million doses fairly across the world. AstraZeneca has also agreed to supply the Serum Institute of India with 1 billion doses for low and middle-income countries, with a commitment to provide 400 million before the end of 2020.17
The company has indicated that as many as 30 million doses could be available in Britain as early as September 2020 and the U.S. could begin receiving supplies of the ChAdOx1 nCov-19 vaccine as early as October.18