U.S. health agencies continue to recommend additional COVID-19 vaccine doses for children, yet research suggests booster vaccinations do not provide healthy children with additional immunologic protection against symptomatic infection.
Study Details
Researchers examined 110 children aged 5 to 12 years over the course of a year to determine how long SARS-CoV-2 spike (S)-binding IgG neutralizing antibodies, memory B cells (MBCs), and T cells last in children with no previous history of COVID-19 infection following mRNA vaccination.In the study, researchers analyzed the effectiveness of different combinations of infection and vaccination in producing hybrid immunity against COVID-19.
The study period coincided with the emergence of the Omicron variant when most of the adult population had already been fully vaccinated, providing researchers with a unique opportunity to look at vaccine-induced and hybrid adaptive immunity in those with symptomatic Omicron infection.
According to the study, within six months of the first Pfizer dose, 76 vaccinated children were infected with SARS-CoV-2. Of these, 16 children were symptomatic and received a second dose within three months of infection. The remaining 60 children acquired COVID-19 after having completed a two-dose vaccine series 21 days apart. Of these, 49 children were symptomatic and 11 were asymptomatic.
Of those with asymptomatic infection, only 37 percent had serological evidence of infection, whereas 43 percent had evidence of infection when looking at T cell responses. The researchers noted that this is why using both criteria to identify infections in asymptomatic individuals is important.
Researchers then examined infection rates before and after the completion of the two-dose series to see if children developed symptoms and if this affected the level of hybrid immunity compared to a group of vaccinated children who never had COVID-19.
They found that hybrid immunity was more robust when infection occurred after completing the two-dose primary series but before booster vaccination. Additionally, those with symptomatic infection had a stronger antibody response than those with asymptomatic infection, although both groups had comparable T cell responses.
Of the 76 children who acquired hybrid immunity, researchers found that those who received a booster had higher antibody titers, a test that measures the level of antibodies in a blood sample. However, the increase was small compared to the change observed between the first and second vaccine doses. Moreover, there was “little to no immunogenic benefit” based on the responses measured in boosted children who previously had COVID-19 and were vaccinated.
Notably, neutralizing antibodies produced after vaccination were well below those of children with hybrid immunity, which was the only group with antibody titers above the threshold associated with protection from symptomatic infection. This means that even though children may have developed antibodies after receiving a vaccine, they were not necessarily protected against symptomatic infection.
FDA Uses Antibodies to Gauge Vaccine Protection
Neutralizing antibodies against SARS-CoV-2 have been widely used to infer protection against COVID-19, despite the U.S. Food and Drug Administration’s (FDA) acknowledgment early on that antibody levels alone were not predictive of protection. Moreover, both Pfizer and Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, have admitted there is no defined standard of correlate protection, which refers to the level of antibodies needed to confer protection.During the meeting, Dr. Paul Offit, director of the Vaccine Education Center and professor of pediatrics in the Division of Infectious Diseases at Children’s Hospital of Philadelphia, and Dr. Hank Bernstein, professor of pediatrics at Zucker School of Medicine, raised concerns over how effectiveness was being measured.
Dr. Ofer Levy, a VRBPAC member and an infectious disease physician at Boston Children’s Hospital, voted “yes” to change the computation of COVID-19 boosters even though Pfizer admitted there is “no established correlate of protection.”
Dr. Levy then asked the FDA what their “overall approach” would be to improve the understanding of correlate protection.
“We spend a good amount of time reviewing antibody data. We have no doubt antibody data is important. We don’t have a level of antibody that anybody is comfortable stating is correlated [with] protection,” he said.
Dr. Levy said antibodies are essential, and looking at T cell responses may be “trickier,” but federal leadership would be needed to standardize the T cell assay and “encourage or, in fact, require” vaccine sponsors to gather that information.
“This is an effort that’s critical not just now but for future cycles of vaccine revision. If we aren’t able to define a standard for correlate protection, we are fighting with one arm tied behind our back,” Dr. Levy added.
Dr. Marks acknowledged Dr. Levy’s question but said it was easier initially to look at antibodies instead of T cell-mediated immunity.
“We have been having conversations with our colleagues at the NIH [National Institutes of Health] and throughout government about how we might move forward here,” Dr. Marks said. “It is something that we don’t have an answer to yet.”
Dr. Marks said as vaccines are developed in the future, it would “become even more important” to define a standard of correlate protection because “we won’t be able to have a large naive population to vaccinate with newer vaccines.”
“We will need to understand the T cell response better,” Dr. Marks said. “I take your point; it’s just that we haven’t solved the problem yet.”
The Epoch Times contacted the FDA for comment.
