Clinical trial data for Pfizer’s maternal vaccine to protect babies from RSV support the vaccine’s safety and efficacy, according to a vote by an FDA advisory committee. The FDA could soon approve the vaccine. But a popular social media post makes misleading claims about the trial findings.
Update, Sept. 25: The FDA approved Pfizer’s maternal vaccine, Abrysvo, on Aug. 21 for pregnant individuals at 32 to 36 weeks of gestation. On Sept. 22, the CDC recommended the vaccine at those stages of gestation on a seasonal basis, meaning pregnant people would get it if their babies would be born during the RSV season.
Respiratory syncytial virus, or RSV, causes a mild cold for most people, but infants – particularly young and premature babies – can experience severe infections. However, a vaccine to protect young babies could soon get approval by the Food and Drug Administration.
Building on a scientific breakthrough in the study of RSV about a decade ago, Pfizer has developed a maternal vaccine, to be given to pregnant people so that the antibodies they develop can be passed on to their babies. The results of the clinical trial, published in the New England Journal of Medicine, showed a vaccine efficacy of 81.8% against severe RSV-confirmed lower respiratory tract illness requiring a medical visit in the first 90 days after birth and an efficacy of 69.4% through 180 days after birth.
The vaccine is the same formulation as Pfizer’s RSV vaccine for older adults, who also are susceptible to serious and dangerous illness from the virus. The FDA approved the vaccine for adults age 60 and older on May 31, but it must separately consider the data on administering the shot in pregnant people to protect babies. On May 18, an FDA advisory committee voted affirmatively that the trial data supported the effectiveness and safety of the vaccine. The FDA’s decision on whether to approve it is expected to come in August, Pfizer said.
As we’ve explained in a Q&A article, RSV infects nearly all kids by the time they’re 2 years old, the Centers for Disease Control and Prevention says. In addition to young and premature babies, infants with heart or lung disease, or weakened immune systems are particularly prone to severe illness. Dr. Mary T. Caserta, a professor of pediatrics at the University of Rochester Medical Center and a member of the American Academy of Pediatrics’ Committee on Infectious Diseases, told us the virus “is the most commonly identified cause of lower respiratory tract disease (pneumonia and bronchiolitis)” in infants. And “RSV bronchiolitis is the single most common cause of hospitalization in the first year of life in the US,” she said in an email.
Given the volume of misinformation that has circulated on social media regarding the COVID-19 vaccines, it may not be surprising that posts are beginning to appear questioning the safety of the RSV vaccine. One popular post, from a social media account that frequently posts about vaccines, raised “concerns,” but some of its claims are misleading or require more context.
One slide in the Instagram post listed percentages for adverse events reported in Pfizer’s clinical trial after vaccination, but it didn’t explain that the percentages were similar for those in the placebo group. And these adverse events are any health events that occur after vaccination, not necessarily events caused by the vaccine.
The peer-reviewed trial results said: “No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively).”
Bar graphs published with those results show the percentages were also similar for events considered “serious” or “severe.” (Similar bar graphs were part of a Pfizer presentation to a CDC advisory board. See slides 19 and 20.)
Natalie Dean, assistant professor in the Department of Biostatistics & Bioinformatics at the Emory University Rollins School of Public Health, told us that people, and particularly pregnant women, can have adverse events — regardless of whether they received a vaccine. “There’s a lot going on in their health,” she said. “A big strength of randomized trials is that we can separate out how often do these things happen at baseline for a placebo group … and then compare that with the vaccination group.” That comparison can “disentangle if there was any increase in adverse events that can be attributed to the vaccine.”
The phase 3 trial enrolled nearly 7,400 pregnant participants in 18 countries, with half receiving the vaccine and half getting the placebo; 45% of participants were in the United States. For the infants, 7,128 continued with the study and are being followed for up to 24 months of age.
There were very few adverse events that were considered to be related to the Pfizer vaccine. The FDA briefing document on the vaccine said that within 30 days after vaccination, 0.4% of adverse events reported in the vaccine group and 0.1% of adverse events in the placebo group were considered to be related to the injection by the investigator.
There were two adverse events from delivery through 1 month later that were “possibly” related to the vaccine, the briefing document said. One was eclampsia, or seizures that can occur in pregnancy, 15 days after vaccination, and the other was one premature delivery that resulted in a normal birth. Since there was no other cause for the premature delivery, the investigator leading the study said it would be “handled as related to” the vaccine.
Three other serious adverse event cases that occurred in the vaccination group through six months after delivery were considered to be related by the investigator: “[s]evere pain in multiple extremities,” which was resolved six days later; premature labor, which resolved in a day and resulted in a full-term pregnancy; and a case of lupus, with thrombocytopenia, a condition of low platelet count in the blood, attributed to the lupus.
For the infants, no serious adverse events “were considered related to maternal vaccination,” the briefing document said. But in one case of an infant death, the investigator assessed that it wasn’t related to vaccination while the FDA was “unable to exclude the possibility of the extreme prematurity and subsequent death being related.”
In all, there were five infant deaths (0.1%) in the vaccine group and 12 (0.3%) in the placebo group.
In its briefing document, the FDA said there was a “numerical imbalance of 1%” in premature births between the vaccine and placebo groups, noting that the difference was not statistically significant. In the vaccine group, 5.7% of participants had a preterm birth, compared to 4.7% of the placebo group.
The difference for low birth weight also wasn’t statistically significant: 5.1% in the vaccine group and 4.4% in the placebo.
The Instagram post described this as “about 20% more preterm babies and low birth weight babies” in the vaccine group. There is a 20% difference between the two groups for the number of preterm births, but the figure requires context.
As we said, the difference for preterm births wasn’t statistically significant, though the FDA indicated its advisory committee — the Vaccines and Related Biological Products Advisory Committee — could discuss the imbalance in its May 18 meeting, which the committee did.
The rates of preterm birth in the trial were lower than the background rate of 10% of all births globally for 2020.
One premature birth was assessed to be “possibly related” to the vaccine. That’s the case mentioned above, in which the infant had “a normal birth outcome and no complications,” the FDA said. And, as we said, the FDA was “unable to exclude the possibility” that prematurity and the subsequent death of another infant were related to the vaccine.
About 90% of the preterm births in both the vaccine and placebo groups occurred at 34 to 37 weeks’ gestation (a full pregnancy is 38 to 42 weeks). That means most of the preterm births were only mildly premature, or what’s called “late preterm.” For what’s considered “extremely preterm birth,” which is less than 28 weeks, there was one infant in the vaccine group and one in the placebo.
The FDA advisory committee did discuss the preterm birth imbalance. While the vote was unanimous that the data supported the effectiveness of the vaccine, the vote was 10-4 on whether the data supported the safety. The committee members who voted “no” expressed concern about the data not providing enough certainty on whether the imbalance in preterm births was a safety issue.
One reason for the concern is that another pharmaceutical company, GSK, had voluntarily halted clinical trials of its maternal vaccine candidate due to an imbalance in preterm births. That imbalance wasn’t statistically significant in high-income countries in the trials, but it was in low- and middle-income countries, as we’ve written.
In the advisory committee meeting, Dr. Paul A. Offit, a vaccine expert and pediatrician at the Children’s Hospital of Philadelphia, asked whether the data was “adequate in terms of reassuring one that what was seen with GSK’s vaccine is not going to be seen here.” Offit said, “If you’re in any sense risking premature births with this vaccine, I think there’ll be a big price to pay, and so I guess I just don’t feel we have enough data to be reassuring.”
Others who voted in favor of the data supporting the safety of the vaccine noted that the imbalance in Pfizer’s trial wasn’t statistically significant.
Update, Aug. 22: The FDA approved Pfizer’s vaccine, called Abrysvo, on Aug. 21. The FDA said the prescribing information will include a warning telling health care providers to administer the one-dose injection at 32 through 36 weeks of gestation in order to avoid a potential risk of preterm birth before 32 weeks. Because of the numerical imbalance in preterm births in the trial, the FDA said, “[t]he available data are insufficient to establish or exclude a causal relationship between preterm birth and Abrysvo.”
Pfizer will be required by the FDA to conduct additional studies to assess the potential risk of preterm birth as the vaccine is rolled out.
Vaccine Doesn’t Contain the Virus
The Instagram post also highlighted a description of the placebo from the FDA briefing document that said the placebo was similar to the vaccine formulation “minus the active ingredients.” The post pointed to those words and misleadingly commented, “basically everything but the virus.”
It’s possible some may wrongly conclude from the post that the vaccine could infect people with the virus. It can’t.
Pfizer’s RSV vaccine is a protein subunit vaccine, which uses part of a protein of a virus, not the whole virus. Other vaccines, including those for hepatitis B and pertussis, are also protein subunit vaccines.
The RSV vaccine is made from pre-fusion F protein from RSV-A and RSV-B, subgroups of the virus. The pre-fusion F protein prompts an immune response in the body, but this fragment can’t cause RSV disease.
Pfizer’s vaccine, as well as other RSV vaccines, including one from GSK that also has been approved for older adults, target the pre-fusion F protein, thanks to scientific research published in 2013 by a team of scientists at the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health. The scientists were able to stabilize the pre-fusion form of the virus’s F protein, which the virus uses to enter human cells, and determined that targeting that form — as opposed to the post-fusion form the protein takes once it fuses with cells — produced highly protective antibody responses.
Another option for protecting babies from RSV illness is also being evaluated by the FDA this year. A monoclonal antibody from Sanofi and AstraZeneca would be given as a single shot to newborns or infants before their first RSV season. The drug, which targets the pre-fusion F protein, was approved by the European Commission in 2022.
The FDA’s advisory committee — VRBPAC by its acronym — is made up of experts in infectious diseases, immunology, pediatrics, biostatistics and epidemiology. Those experts voted unanimously, 14-0, that the clinical trial data supported the effectiveness of the Pfizer maternal vaccine in preventing RSV lower respiratory tract disease and severe disease in babies from birth to age 6 months.
But a slide in the Instagram post featured a quote from a cardiologist, Dr. Peter McCullough, suggesting the data weren’t sufficient to show the vaccine was effective. McCullough, who has made false and misleading claims about the COVID-19 vaccines, first made these comments to a publication of Children’s Health Defense, a group that has spread vaccine misinformation and was founded by Robert F. Kennedy Jr. (Kennedy has taken a leave of absence from his position as chairman of the group to run for president of the United States.)
McCullough said the trial showed “only theoretical efficacy in babies” and that “less than 2% of infants at any time point contracted RSV.”
The trial didn’t measure all cases of RSV, but rather those that required medical attention from a health care provider and included rapid breathing, low blood oxygen and/or chest indrawing (see slide 24). Up to 180 days after birth, 2.5% of all infants in the trial had such a case of medically attended RSV.
In the vaccine group, 57 infants had medically attended RSV lower respiratory tract disease, compared with 117 cases in the placebo group. Those figures show an efficacy of 51.3%, meaning the vaccine cuts the risk of such disease by more than half.
The trial also measured cases of severe illness, which included more severe symptoms during a medically attended visit, being given mechanical ventilation or supplemental oxygen therapy, and certain ICU admissions. At 180 days, there had been 19 cases in the vaccine group and 62 in the placebo group, for an efficacy of 69.4%. At 90 days after birth, efficacy was even higher — 81.8%. (These figures are in Table 7 and 8 of the FDA briefing document.)
The case numbers might sound low to the general public, but they are sufficient to show vaccine efficacy — and scientists don’t expect to see very large figures in a trial, Dean, the biostatistician at Emory University, told us.
“We give vaccines to healthy people to prevent events that we hope are rare,” Dean said, and that’s why clinical trials need to enroll a lot of people. “We know the event itself is rare. But we just need to observe enough data to tell that the differences in rates of disease are real between the groups.”
The numbers may seem small, “but they’re big enough for statistics,” Dean said.
In his quote, McCullough also said RSV in infants is “uncommon,” “low-risk” and “easily treatable with nebulizers.”
But RSV is common in children and “causes a significant burden of disease,” Caserta, the American Academy of Pediatrics committee member, told us. While many infants will only have a cold from RSV, it can be dangerous for some.
As we said, the CDC says nearly all children will get RSV by the time they’re 2. Caserta also said studies have shown that over half of kids are infected by the age of 1.
Dr. Rebecca Schein, a pediatric infectious disease specialist with Michigan State University and an assistant professor at the university, noted that RSV “was part of the so-called triple demic that was filling hospitals last fall.” She told us: “RSV epidemics occur every fall and result in huge numbers of hospitalizations.”
The CDC estimates that 58,000 to 80,000 children under 5 are hospitalized each year because of RSV and that among every 100 babies under 6 months of age with RSV, 1 to 2 may need hospitalization. There are half a million emergency department visits and 1.5 million visits to outpatient clinics for kids under 5 each year. Deaths are “uncommon” in the U.S. — an estimated 100 to 500 each year for kids under 5, though the CDC says RSV-associated deaths are likely undercounted due to a lack of testing. In lower-income countries, death in infants is more of a concern; an estimated 45,700 babies up to 6 months of age worldwide died due to RSV in 2019, according to a systematic analysis of hundreds of studies published in the Lancet.
In addition to preventing hospitalizations and deaths from RSV through vaccination, “the bigger goal is to improve overall lung health of infants,” Dr. Barney S. Graham, a professor at Morehouse School of Medicine who was one of the leaders of the NIAID team that found the breakthrough on the RSV F protein, told Science in November. “If they’re infected with RSV very early in life and develop severe disease, that affects their lung development and overall lung health probably for their lifetime. So the goal here is to really improve overall lung health and that is something that’s hard to calculate until you’ve seen it evolve over several years.”
As for using a nebulizer, which changes liquid medicine into a mist that can be inhaled, Caserta said that a variety of nebulized treatments had been studied to relieve RSV symptoms, but “no clear benefit for preventing hospitalization or reducing hospital stay has been uniformly demonstrated.”
“There is no specific therapy for RSV infection,” she said. “Supportive care with oxygen and IV fluids as needed are the most common interventions used for hospitalized infants.”
Schein said that albuterol “is the most common nebulized medication and is used to treat asthma.” Its use in treating RSV “is minimal and only useful in infants with a predisposition to asthma.”
Finally, McCullough said that “[w]idespread use” of the RSV vaccine “can be expected to cause fetal loss in some unfortunate women,” but the clinical trial didn’t include any fetal losses due to vaccination.
In the trial, there were 10 fetal deaths in the vaccine group and eight in the placebo group, the FDA briefing document said. These were due to “various clinical conditions and presentations.” The FDA agreed with the assessment of the study investigator that none was related to the vaccine, “based on review of available case narratives and evident lack of temporal relation of vaccination to the fetal loss events.”
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