Respiratory syncytial virus (RSV) in pediatric patients remains a significant global burden, especially in hospitalized patients, but research, maternal vaccination and future efforts provide a way to combat and prevent future outbreaks, study finds published in Pediatric respiratory exams.1
In young children, RSV remains a leading cause of hospitalization, bronchiolitis, and pneumonia. The burden of RSV is high, with an estimated 33 million lower respiratory infections, 3.6 million hospital admissions, and 101,400 RSV-associated deaths annually worldwide among children under 5 years of age. . Additionally, in 2017, the estimated global costs of RSV-related infections were over €4.8 billion.
A team of researchers from the Montreal Children’s Hospital-McGill University Health Center in Canada conducted a review of previous, current and ongoing research efforts for pediatric RSV immunization.
RSV, like all members of the pneumoviridae family, is a negative-sense, single-stranded RNA virus. Two transmembrane glycoproteins composing its bilipid envelope, the attachment protein G and the fusion protein F, are responsible for neutralizing host antibodies. While the G protein attaches the virus to host hair cells in the respiratory tract, the F protein allows the virus to fuse with host cell membranes. RSV is divided into subtypes A and B based on its antigenic variability in response to monoclonal antibodies (mAb), with greater variability in glycoprotein G binding. Significant variability in glycoprotein G makes development difficult a vaccine; however, the F fusion protein is more similar between viral strains and is the preferred protein used in the development of immune therapies.
In 1998, the United States Food and Drug Administration approved palivizumab, the first humanized mAb targeting the F protein. It is used in many high-income countries to protect against serious RSV infections in areas where populations are at higher risk. Although indications vary by country, palivizumab is primarily used to treat premature infants with or without bronchopulmonary disease as well as infants with hemodynamically significant congenital heart disease.
Although several clinical trials have improved the efficacy of this mAb, monthly palivizumab injections are necessary during the RSV season to maintain an active mAb in circulation. “This requires significant resources from families and healthcare teams, particularly with interseasonal RSV activity during the COVID-19 pandemic,” the review authors added.
Nirsevimab, a new mAb, has been approved in the United Kingdom and North America to prevent RSV in newborns and infants. It targets the pre-F protein and has a prolonged half-life compared to palivizumab and therefore requires only a single dose during an RSV season. Several ongoing clinical trials, including the Evaluation of Safety and Efficacy of Nirsevimab in Healthy Preterm and Term Infants in China (CHIMES; NCT05110261) and prevention of hospitalized anti-RSV monoclonal antibodies (HARMONIE; NCT05437510) are studying outcomes in healthy preterm and term infants.
“In addition, a third mAb with a structure similar to that of nirsevimab is currently in phase 3: clesrovimab (ClinicalTrials.gov Identifier, NCT04938830) recruiting 1,000 children under one year of age in several countries around the world,” noted authors.
Despite ongoing research into the treatment of neonates and infants, there are no approved vaccines for active RSV immunization in children, although “several clinical trials are currently in early phases (phases 1 and 2) for active immunization in children using live attenuated viruses. nucleic acids (messenger RNA) and recombinant vector vaccines,” the authors noted.
There are, however, two newly approved vaccines for adults over 60 years of age, both consisting of bivalent protein subunits of the stabilized pre-F protein of antigenic groups A and B. The vaccines have been approved in the United States, Canada and Europe. since 2023 and phase 3 trials in progress (RENOIR, NCT05035212) are evaluating the safety, immunogenicity and effectiveness of this treatment in adults.2
A final vaccination option mentioned by the authors was that of maternal vaccination. “The goal is to increase the infant’s serum antibody concentration after birth by increasing transplacental transfer of antibodies,” they wrote. Although successful transplacental transfers of RSV antibodies have been recorded, the correlation between antibody concentration and severity of disease onset is still unclear. A recent trial using the approved stabilized pre-F vaccine showed promising results for infants with severe RSV-associated lower respiratory tract illnesses, but did not show statistical significance for RSV-associated lower respiratory tract infections followed medically.
Further research and results from ongoing clinical trials in different age groups will help guide vaccination recommendations to combat and prevent RSV.
