In young children, the Pfizer/BioNTech and Moderna COVID-19 vaccines are expected to primarily protect against severe disease. Both shots successfully met the set benchmarks for vaccine effectiveness, which involved comparing antibody responses to those of adults. Online posts critical of government recommendations for the pediatric vaccines, however, fail to mention these essential data.
In June, the Food and Drug Administration authorized the first COVID-19 vaccines for young children: a three-dose Pfizer/BioNTech vaccine, for kids 6 months old through 4 years of age, and a two-dose Moderna vaccine, for 6 months through 5 years of age.
Both vaccines, which use messenger RNA, or mRNA, to trigger a protective immune response against the coronavirus, are smaller-dosed versions of the companies’ vaccines for adults, which were found in large, randomized controlled trials to be effective. Real-world evidence also has repeatedly shown the vaccines provide strong protection against severe disease.
As with the authorizations for other children, the primary way the FDA evaluated the COVID-19 vaccines for young kids for effectiveness was through a comparison of the children’s antibody responses to those of adults. If a similar percentage of vaccinated children produce antibodies — and in similar amounts — to vaccinated adults, then it can be inferred that the kids’ vaccine is also effective. This approach, known as immunobridging, is an established method that has been used for other vaccines, including those given to children.
Importantly, the pediatric trials were designed as immunobridging studies from the start — and were not necessarily meant to be able to provide good efficacy estimates of how well the vaccines prevent infection or symptomatic disease.
This is especially relevant because with the rise of the highly transmissible and more immune-evasive omicron variant, scientists don’t expect the vaccines to be very good at averting infections or mild illnesses. Instead, the vaccines are primarily useful in preventing severe disease.
An online post critical of the shots for young children, however, misleadingly skips over all of that. Instead, it calls Pfizer’s and Moderna’s data “extremely weak” and “inconclusive” and only mentions the lackluster or uncertain efficacy estimates from the studies, which were conducted during the omicron era.
“In the subgroup of children aged six months to two years, the trial found that the vaccine could result in a 99% lower chance of infection—but that they also could have a 370% increased chance of being infected,” the post said about the Pfizer/BioNTech vaccine. “In other words, Pfizer reported a range of vaccine efficacy so wide that no conclusion could be inferred. No reputable medical journal would accept such sloppy and incomplete results with such a small sample size.”
The piece, which was a July 14 guest post on former New York Times opinion columnist Bari Weiss’ Substack page, went on to feature Moderna’s efficacy figures, which it called “very weak” or “low.”
The reported efficacy numbers are correct (or nearly so — one of the Moderna figures is not the primary efficacy number). But as we said, that was not the only or even the main information regulators and outside experts used to evaluate the effectiveness of the vaccines. And as a former FDA official told us, focusing on those numbers misses the point.
“The critical thing in this is that even if the vaccines aren’t very effective in protecting against mild disease … that doesn’t mean they won’t be effective in protecting against severe disease,” Dr. Philip Krause, former deputy FDA chief for vaccines, said in a phone interview. “That was really the FDA’s goal in making the vaccines available.”
The Substack post was co-authored by Dr. Marty Makary, a surgeon and public policy researcher at the Johns Hopkins School of Medicine who has previously spread misleading or unsupported information about COVID-19, and Dr. Tracy Beth Høeg, a physical medicine and rehabilitation physician in private practice in California. Høeg is also a consultant epidemiologist for the state of Florida, which is the only state to recommend not vaccinating healthy children against COVID-19.
On Twitter, Makary criticized the use of “immunobridging,” saying there was “no justification to bypass rigorous safety & efficacy clinical trials in children.”
But as we’ve explained in our guide to the COVID-19 vaccines for the youngest children, the plan from the start was to use immunobridging to infer that the COVID-19 vaccines would work similarly well in children as adults.
“The FDA established with the companies immunobridging criteria to show that the immune responses in these children would be at a level that would likely give comparable protection to what was observed in older people,” said Krause. “And that’s something that’s been done for many other vaccines.”
Immunobridging between children and adults has been used to approve Vaxchora, a cholera vaccine, Krause said, and the method was also used to approve two HPV vaccines down to age 9. Immunobridging from a different flu vaccine tested in children also served as the basis for approving the seasonal flu vaccine Afluria in kids, he added.
“Immunobridging is a common way to extend an existing vaccine into new populations,” Natalie Dean, a biostatistician at Emory University who specializes in methods evaluating the effectiveness of vaccines, told us in an email. “We leverage the extensive efficacy and safety data from other populations, and so do not need to start from scratch in generating evidence.”
Dr. Paul A. Offit, a vaccine expert and pediatrician at the Children’s Hospital of Philadelphia and a member of the FDA’s advisory committee, previously told us that the large confidence intervals for the Pfizer/BioNTech vaccine’s efficacy figures meant that little could be concluded from them — but that the antibody data was “excellent” and “enough” to know that the vaccine is likely to work.
He confirmed to us that the data that “convinced” the FDA to authorize the COVID-19 vaccines for little kids was the immunobridging data.
“Specifically, that the titer of neutralizing antibodies found after vaccination was virtually identical to those titers found in the 18-25-year-old age groups where protection against severe disease was excellent,” he said in an email.
Trial data show that compared with young adults, little kids responded equally well if not slightly better to the vaccine. All or nearly all vaccinated children mounted a neutralizing antibody response against the coronavirus — and at levels comparable if not a bit higher than those of adults (or in Pfizer’s case, 16-to-25-year-olds; see tables 12-15 for Pfizer/BioNTech and tables 55, 56, 79 and 80 for Moderna).
In the evaluations, the efficacy information was supplemental. In the case of Moderna, the data are consistent with some, albeit less, protection against symptomatic infection with the omicron variant compared with earlier variants — a 50.6% reduction in risk for babies and toddlers and a 36.8% risk reduction for kids 2 through 5 years old.
As we’ve noted before, the Pfizer efficacy figures against symptomatic infection were actually higher than Moderna’s — 75.6% for babies and young toddlers and 82.4% for 2- to 4-year-olds — but were highly uncertain.
As Krause told us, though, “the intent of the study wasn’t to come up with that answer.”
“The study was not designed to determine … the efficacy against disease. The study was designed as an immunobridging study,” he said. Because few kids fell ill, “what that meant was that they couldn’t come up with a clear estimate of how effective the vaccine was against what would have mostly been mild disease.”
Krause acknowledged that immunobridging is “imperfect,” since the evaluations typically hinge on more easily measured antibodies, and don’t capture cell-mediated immunity, such as that from T cells. But, he said, the sort of immunobridging used for the COVID-19 vaccines “is something I think most people in vaccinology would not consider to be very controversial.”
The FDA has already been using immunobridging in its COVID-19 vaccine authorizations. Krause noted that in May 2021, the FDA used immunobridging to make the Pfizer/BioNTech COVID-19 shot available to teens 12 to 16 years old. It again used immunobridiging in its authorization of the Pfizer/BioNTech vaccine for kids 5 to 11 years old, as we’ve written.
Subsequent studies, Krause said, “showed that the vaccine authorized on the basis of this immunobridging approach is protecting children against severe disease.” In March, a study published in the New England Journal of Medicine found that the Pfizer/BioNTech vaccine “reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age.”
Protection Against Severe Disease
Indeed, Krause emphasized that the purpose of vaccination is to prevent severe COVID-19 — and that the Substack post is “confusing the notion of working well against mild versus severe disease.”
“Looking at results from mild disease isn’t really giving us a very good picture of how effective the vaccine is and how well it’s doing what it needs to do,” he said, “because the vaccines are being recommended for the purpose of protecting against severe outcomes.”
Krause, who is mentioned in the Substack post, retired from the FDA in November. He penned an op-ed with another departing FDA official and Offit that criticized the agency’s decision to allow healthy younger adults to receive booster shots, given evidence that two doses of the mRNA shots remained protective against severe illness. (We wrote about the booster controversy in September.)
But Krause said he agreed with the FDA’s decision to authorize the vaccine for little kids. He also agreed with the CDC’s recommendation that all children be vaccinated, although he thought the agency could better convey the risks of COVID-19 to children and how the vaccine would benefit kids.
“Some children,” he said, “stand to benefit considerably more than others” — and for them, the “degree of urgency” for vaccination is higher.
Krause noted that severe COVID-19 and related complications, like MIS-C, are rare among children — and are likely even less of a risk now than they were earlier in the pandemic. Still, he said, those events do occur, and given the safety of the vaccine, “the benefits will outweigh the risk.”
“Certainly any child who has risk factors for severe disease, it’s really a no-brainer” to get vaccinated, he said. “But even for children who don’t have these risk factors, it’s certainly a very reasonable decision to get them vaccinated.”
Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over FactCheck.org’s editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.
“Coronavirus (COVID-19) Update: FDA Authorizes Moderna and Pfizer-BioNTech COVID-19 Vaccines for Children Down to 6 Months of Age.” Press release. FDA. 17 Jun 2022.
McDonald, Jessica. “A Guide to COVID-19 Vaccines for the Youngest Kids.” FactCheck.org. 7 Jul 2022.
“Vaccine efficacy, effectiveness and protection.” WHO. 14 Jul 2021.
“FDA Briefing Document, EUA amendment request for Pfizer-BioNTech COVID-19 Vaccine for use in children 6 months through 4 years of age.” Vaccines and Related Biological Products Advisory Committee Meeting on 15 Jun 2015.
“FDA Briefing Document, EUA amendment request for use of the Moderna COVID-19 Vaccine in children 6 months through 17 years of age.” Vaccines and Related Biological Products Advisory Committee Meeting on 14-15 Jun 2015.
Krause, Philip. Former Deputy Director, Office of Vaccines Research and Review at FDA’s Center for Biologics Evaluation and Research. Phone and email interview with FactCheck.org. 21 Jul 2022.
“Misleading Wall Street Journal opinion piece makes the unsubstantiated claim that the U.S. will have herd immunity by April 2021.” Health Feedback. 26 Feb 2021.
“Fox News article listing alleged mistakes in COVID-19 public health response mixes accurate information with unsubstantiated claims.” Health Feedback. 23 Mar 2022.
Smith-Schoenwalder, Cecelia. “DeSantis Makes Florida an Outlier on Coronavirus Vaccines for Young Children.” U.S. News & World Report. 17 Jun 2022.
Carlson, Tucker. “Tucker Carlson: Politicians are continuing to use COVID as a pretext to force their agendas.” Fox News. 14 Jul 2022.
Makary, Marty (@MartyMakary). “Inferred through “immunobridging” young adult data from another study?? This is statistical acrobatics, which appears to be done to achieve a desired outcome. There is no justification to bypass rigorous safety & efficacy clinical trials in children.” Twitter. 14 Jun 2022.
Dean, Natalie. Assistant professor, Biostatistics and Bioinformatics, at Rollins School of Public Health at Emory University. Email sent to FactCheck.org. 21 Jul 2022.
Offit, Paul A. Director of the Vaccine Education Center, Division of Infectious Diseases at Children’s Hospital of Philadelphia. Email sent to FactCheck.org. 20 Jul 2022.
“FDA Briefing Document, Licensure and Emergency Use Authorization of Vaccines to Prevent COVID-19 for Use in Pediatric Populations.” Vaccines and Related Biological Products Advisory Committee Meeting on 10 Jun 2022.
Price, Ashley M. et al. “BNT162b2 Protection against the Omicron Variant in Children and Adolescents.” NEJM. 30 Mar 2022.
Brennan, Zachary. “Turmoil at CBER: Peter Marks grabs control of FDA’s Office of Vaccines ahead of 2 key career leader departures.” Endpoints News. 28 Sep 2021.
Krause, Philip et al. “We don’t need universal booster shots. We need to reach the unvaccinated.” Washington Post. 29 Nov 2021.
McDonald, Jessica. “Biden’s Controversial COVID-19 Vaccine Booster Plan.” FactCheck.org. 3 Sep 2021.