US has 'embarrassment of riches' to protect children from RSV
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This is the second respiratory disease season with two new powerful tools to protect infants from severe respiratory syncytial virus disease, and experts are optimistic that uptake will improve from last season.
In 2023, the FDA approved nirsevimab, a monoclonal antibody (mAb), for infants aged up to 24 months — the CDC recommends it up to age 19 months — and a maternal vaccine that can be given to pregnant women between 32 and 36 weeks’ gestational age to protect infants during their first 6 months of life.
“Virtually every single child gets an RSV infection by the time they are 2 years old,” Lori Handy, MD, MSCE, attending physician in infectious diseases and associate director of the Vaccine Education Center at The Children’s Hospital of Philadelphia, said in an interview.
RSV is the leading cause of hospitalization for infants in the United States. Most of the infections are mild and can be managed with outpatient care, but one or two of every 100 children will be hospitalized with a lower respiratory tract infection during their first 6 months of life, according to Handy.
“The worst outcome is some children get such a severe respiratory infection that they need respiratory support through a ventilator,” Handy said. “About 100 to 300 of those very young children will die each year.”
Both new immunizations have been highly effective at preventing severe RSV disease in infants. Research from the CDC’s New Vaccine Surveillance Network showed that nirsevimab was around 90% effective at preventing hospitalization for RSV-associated lower respiratory tract infections, and Pfizer’s phase 3 data showed that its maternal vaccine was more than 80% efficacious against RSV-positive severe medically attended lower respiratory tract illness in infants within 90 days of birth.
“We have no data to suggest that one approach is better than the other,” C. Buddy Creech, MD, MPH, director of the Vanderbilt Vaccine Research Program, and Healio Pediatrics Peer Perspective Board Member, told Healio. “In situations where the pregnant individual is immunocompromised, or in situations of placental pathology where antibody transfer might be affected, nirsevimab makes more sense. But in general, we treat these as equivalent measures to prevent severe RSV in infants.”
‘Many barriers’ to immunization
Both immunizations received FDA approval shortly before RSV season began last fall and encountered barriers during rollout that may have impacted uptake.
“The 2023-2024 RSV season is a hard season to use as a benchmark,” Creech said. “Though we are thrilled with the approval of nirsevimab and maternal immunization just prior to the season starting, we unfortunately had very little time to ensure a successful rollout.”
According to the CDC, uptake of the maternal vaccine was just 17.8% as of Jan. 31, which experts told Healio was lower than they would have liked but not necessarily lower than they expected.
“The CDC and American College of Obstetricians and Gynecologists (ACOG) recommendations came out relatively close to respiratory season, so there was not really a time frame for everybody to gear up and give it that first season,” Kevin A. Ault, MD, FACOG, FIDSA, chair of the department of obstetrics and gynecology at Western Michigan University Homer Stryker MD School of Medicine and member of the ACOG expert group for immunization, said in an interview. “It is about where I would expect it because of all those hiccups.”
Uptake of nirsevimab was much better — 41.3%, according to the CDC — despite a national shortage and other issues related to the rollout. The FDA approved the mAb for infants born during or entering their first RSV season or for infants aged up to 24 months who remain vulnerable to RSV in their second season.
“Demand was actually very high, but supply could not keep up,” Handy said. “There were many barriers, like insurance coverage distribution, that limited the ability for providers to get to all of the babies that had families that wanted coverage.”
A second, more effective mAb
However, Handy believes that nirsevimab coverage will improve this season.
“I am optimistic that we will have fewer logistical challenges,” Handy said,“which allows [providers] to directly care for their patients and move logistics to the side.”
In September, Sanofi announced that the FDA approved a new manufacturing filling line for nirsevimab, which will expand the availability of doses. The company, which developed the mAb with AstraZeneca, also announced the launch of a program for providers to request doses for their practices.
Nirsevimab is available at no cost to families that are uninsured or otherwise unable to pay for it through the CDC’s Vaccines for Children Program.
The CDC recommends administering nirsevimab during RSV season from October through March — ideally in the hospital after birth, or during any health care visit. Because infants are at the highest risk for severe RSV during their first 3 months of life, Handy said pediatricians should recommend nirsevimab to families as early as their first visit.
“This is something you want to administer to a baby as quickly as possible to make sure they are protected during their highest risk period,” she said.
Handy said pediatricians should come up with talking points about nirsevimab that underscore they are recommending it to all infants in their practice as part of routine immunization.
Nirsevimab is not the only mAb approved for the prevention of severe RSV infection in infants. Palivizumab was approved more than 25 years ago to protect children at risk for severe lower respiratory tract infections caused by RSV.
According to the AAP, nirsevimab is preferred over palivizumab because it is more effective and only requires one dose instead of five.
“All around, it's really the right choice to make, logistically, for the family and the practice,” Handy said.
Palivizumab is used in other countries where nirsevimab is not yet approved or recommended. The AAP recommends administering palivizumab if nirsevimab is “not available or not feasible to administer ... until nirsevimab becomes available.” According to the AAP, infants who have received less than five doses of palivizumab should receive a dose of nirsevimab, when available, within 30 days of their last dose of palivizumab because protection from the latter wanes after 30 days.
Children aged 20 to 24 months with a very high risk for serious RSV infection can still receive palivizumab, Handy said, because nirsevimab is recommended only through 19 months of age.
Maternal vaccine recommendations
The maternal RSV vaccine is available to patients from September through January and should be administered from 32 through 36 weeks’ gestation, according to guidelines from ACOG.
“The first step is to offer it,” Creech said. “Patients cannot accept a vaccine they never hear about.”
The CDC recommends that infants whose mothers received the maternal vaccine less than 2 weeks before birth also receive nirsevimab, but otherwise the mAb is not recommended for babies whose mothers received the shot.
If a pregnant woman received a dose of the vaccine during the 2023-2024 RSV season, ACOG does not recommend they get an additional dose in subsequent pregnancies. Instead, providers should recommend nirsevimab for their babies.
Creech said that recommendation may change in the future, though.
“Studies to determine the best interval are underway right now,” he said. “We will also be helped by studies in other regions of the world, like the U.K., where nirsevimab is not recommended [and] mothers are vaccinated during each pregnancy with RSV vaccine.”
‘An embarrassment of riches’
Uptake of nirsevimab was more than double the uptake of the maternal vaccine last year, and there are a variety of reasons this may be, experts said.
“I think the fact that it is a new vaccine always provokes some questions,” Ault said.
Creech noted that misinformation and mistrust is less common with mAbs than vaccines, making nirsevimab more desirable for some people.
“This was definitely the case during COVID-19, when individuals may have been wary of vaccination but did not express safety concerns around monoclonal antibodies,” he said. “At the end of the day, most individuals want the best protection they can have, with the fewest side effects.”
Timing may also have played a role, Handy said. She pointed out that between 32 and 36 weeks’ gestation is not a visit when vaccines are typically administered.
“Not only are we recommending a new product, we are actually recommending an entire new process to be developed for obstetricians,” Handy said.
Obstetricians have traditionally been successful at recommending other vaccines, including shots for influenza and Tdap, Creech said. According to the CDC, influenza vaccine coverage peaked at more than 60% among pregnant women in 2020, and in 2019, nearly 80% of pregnant women received Tdap.
“One of the factors that usually shows in favor of maternal immunization is if it has a newborn benefit — that's usually a point that pregnant people will respond to, [making] uptake more likely,” Ault said.
Ensuring every child is protected against RSV will require obstetricians and pediatricians to work together, Creech said. If a pregnant patient decides not to get the maternal vaccine, obstetricians should inform the child’s pediatrician so they can offer nirsevimab instead.
“The OB-to-pediatrician handoff has never been more important,” Creech said.
After decades of work to develop ways to protect babies from severe RSV infection, providers and patients now have more than one option to choose from — and there may be more on the way.
According to Creech, there are several other products in development to protect infants from RSV, including an mAb developed by Merck that is “pretty far along and poised to contribute first.” Merck released positive topline results from a phase 2b/3 trial for the mAb, clesrovimab, in July. Creech said Sanofi, Moderna, Meissa and others also have products in late-stage development.
“Severe RSV disease is now a preventable illness,” Creech said. “In the U.S., we have an embarrassment of riches to keep infants safe.” – by Sara Kellner
References:
- AAP. Recommendations for the prevention of RSV disease in infants and children. https://publications.aap.org/redbook/resources/25379/AAP-Recommendations-for-the-Prevention-of-RSV. Published Feb. 21, 2024. Accessed Sept. 17, 2024.
- ACOG. Maternal respiratory syncytial virus vaccination. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2023/09/maternal-respiratory-syncytial-virus-vaccination. Updated Aug. 21, 2024. Accessed Sept. 17, 2024.
- CDC. AdultVaxView. https://www.cdc.gov/adultvaxview/about/pregnant-persons.html. Updated July 19, 2024. Accessed Sept. 20, 2024.
- CDC. RSV immunization guidance for infants and young children. https://www.cdc.gov/rsv/hcp/vaccine-clinical-guidance/infants-young-children.html. Updated Aug. 30, 2024. Accessed Sept. 20, 2024.
- CDC. Weekly respiratory syncytial virus (RSV) vaccination dashboard. https://www.cdc.gov/rsvvaxview/data/index.html. Updated Aug 27, 2024. Accessed Sept. 17, 2024.
- Children’s Hospital of Philadelphia. Respiratory syncytial virus (RSV) vaccine and monoclonal antibody. https://www.chop.edu/vaccine-education-center/vaccine-details/rsv-vaccine-monoclonal-antibody. Updated July 31, 2024. Accessed Sept. 17, 2024.
- Merck announces topline results from phase 2b/3 trial of clesrovimab (MK-1654), and investigational respiratory syncytial virus preventative monoclonal antibody for infants. https://www.merck.com/news/merck-announces-topline-results-from-phase-2b-3-trial-of-clesrovimab-mk-1654-an-investigational-respiratory-syncytial-virus-preventative-monoclonal-antibody-for-infants/. Published July 23, 2024. Accessed Sept. 25, 2024.
- Sanofi shipping Beyfortus in U.S. to help protect babies against RSV disease; new manufacturing line approved by FDA. https://www.news.sanofi.us/2024-09-16-Sanofi-shipping-BEYFORTUS-R-in-US-to-help-protect-babies-against-RSV-disease-new-manufacturing-line-approved-by-FDA. Published Sept. 16, 2024. Accessed Sept. 17, 2024.
For more information:
Kevin A. Ault, MD, FACOG, FIDSA, can be reached at kevin.ault@wmed.edu.
C. Buddy Creech, MD, MPH, can be reached at buddy.creech@vumc.org.
Lori Handy, MD, MSCE, can be reached at handyl@chop.edu.
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