Respiratory syncytial virus (RSV) prevention strategies for the 2024-2025 viral respiratory illness season

---

The Canadian Paediatric Society gives permission to print single copies of this document from our website. For permission to reprint or reproduce multiple copies, please see our copyright policy.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis^[1] and one of the most common respiratory viruses infecting infants and young children. By 2 years of age, most children will have been infected^[2]. RSV can cause severe lung infections, especially in young infants, which may require hospitalization and intensive care unit (ICU)-level care, and can be fatal.

While there is no specific treatment for RSV, there are pharmacological measures to prevent infection. Palivizumab (SYNAGIS), a monoclonal antibody, has been approved by Health Canada since 2002 and recommended by the National Advisory Committee on Immunization (NACI) since 2003 for prevention of RSV disease in a select group of high-risk infants^[3][4]. Palivizumab must be administered to at-risk infants every 4 to 6 weeks throughout the RSV season (typically four doses delivered from November through March).

Considering the significant burden of RSV disease, its particular risk for adverse health outcomes in young infants, and the consequent impacts on Canada’s health care system, NACI recommends building toward a universal RSV prevention program for all infants (Figure 1).

Two new strategies have been recently approved and recommended to prevent severe RSV infection in infants^[5]:

1. Nirsevimab (BEYFORTUS; Sanofi Pasteur Ltd.): This monoclonal antibody is administered once during the RSV season and offers direct passive antibody protection for the duration of that season.
2. RSVpreF (ABRYSVO; Pfizer Canada): This vaccine is administered in the third trimester (between 32 and 36 weeks gestation) of pregnancy, to provide infants with passive protection via transplacental antibody transfer to the fetus.

Paediatricians and other health care providers (HCPs) caring for infants and young children have important roles in both advocating for and promoting vaccination, alongside other preventive strategies against severe infections. While provincial/territorial RSV prevention programs using these newer agents are being  established in Canada, HCPs should advocate to ensure that the most vulnerable infants are prioritized for protection.

NACI currently has a preferential recommendation for nirsevimab over RSVpreF vaccine, based on reported efficacy (including duration of protection) and safety data. This preference may be revisited as additional data become available. Efficacy for prevention of RSV infection requiring hospitalization had been reported as 76.8 to 81% at 150 days for nirsevimab^[6][7] and 57% at 180 days^[8] for RSVpreF vaccine at the time NACI published their recommendations in May 2024^[5].

WHO SHOULD RECEIVE MONOCLONAL ANTIBODIES (PALIVIZUMAB/NIRSEVIMAB)?

Palivizumab has been recommended for high-risk infants since 2003, and its use is usually limited to preterm infants (<33 weeks GA) and children <24 months of age with congenital heart disease or chronic lung disease. The administration schedule for palivizumab requires most infants and young children to receive four doses throughout the RSV season^[3]. Current palivizumab programs remain in place in jurisdictions where nirsevimab has not yet been introduced. 

Nirsevimab is a long-acting monoclonal antibody that offers sustained protection during a single RSV season with the provision of one dose. In May 2024, NACI released a statement recommending that nirsevimab be prioritized in the following way:

Priority 1

Those at risk for severe RSV disease or who, in the event of severe RSV disease, may face significant limitations to accessing the required critical care support, including

• Infants born during or infants entering their first RSV season who:
  • have risk factor(s) for severe RSV disease (per Box 1)
  • were born before 37 weeks gestational age (GA)
  • face complex transportation issues for treatment of severe RSV disease and/or whose risk of severe RSV disease intersects with established social and structural health determinants such as those experienced by some Indigenous communities across First Nations, Inuit, and Métis populations
• Infants entering their second RSV season whose medical condition continues to place them at ongoing risk for severe RSV disease (per Box 1)

Priority 2

• Providing nirsevimab pricing allows this preventive strategy to be cost-effective, NACI recommends considering nirsevimab for any infant younger than 8 months of age entering (or born during) their first RSV season through universal immunization programs.

Box 1. Definition of infants at increased risk of severe RSV disease

Infants at increased risk of severe RSV disease during their first RSV season:

• All premature infants (i.e., born less than 37 weeks gestational age (GA))* • Chronic lung disease, including bronchopulmonary dysplasia, requiring ongoing assisted ventilation, oxygen therapy, or chronic medical therapy in the 6 months prior to the start of the RSV season • Cystic fibrosis with respiratory involvement and/or growth delay • Hemodynamically significant chronic cardiac disease • Severe immunodeficiency • Severe congenital airway anomalies impairing clearing of respiratory secretions • Neuromuscular disease impairing clearing of respiratory secretions • Down syndrome

Infants at ongoing risk of severe RSV disease during their second RSV season:

• All those listed above, except for infants born at less than 37 weeks GA* and infants with Down syndrome who do not have another medical condition listed above.

^{* Although preterm infants <37 weeks GA qualify for nirsevimab, this is not the case for palivizumab, where preterm infants >33 weeks GA do not qualify[5].} 

The prioritization as outlined by NACI derives from a model-based economic analysis evaluating administration of nirsevimab to all infants, which was found not to meet the cost-effectiveness threshold at this time. However, limiting to Priority 1 has been found to meet this threshold and is therefore the current NACI recommendation. Should the cost of nirsevimab decrease, a universal infant program may become cost-effective.

Evidence from the first year of nirsevimab use in the United States^[9] demonstrated 90% effectiveness in preventing hospitalization due to RSV for infants in their first RSV season. In Galicia, Spain, nirsevimab was found to be 82% effective^[10].

Studies comparing nirsevimab to palivizumab or placebo found no meaningful differences in serious adverse effects^[5].

WHO SHOULD RECEIVE RSVpreF VACCINE?

RSVpreF is a vaccine approved for administration during pregnancy that can offer protection to infants for their first few months of life via transplacental antibody transfer. RSVpreF has a narrow window for administration (32 to 36 weeks GA), and is most effective if administered at least 2 weeks before delivery^[5].

While NACI is not currently recommending a universal RSVpreF immunization program during pregnancy, pregnant persons may consider RSVpreF vaccination on an individual level to prevent severe RSV disease in their infant’s first few months of life. As more data and information become available over time, NACI’s recommendation around maternal RSV immunization may change. Evidence-based information to inform decision-making around RSVpreF immunization should be offered by prenatal care providers.

When RSVpreF is administered during pregnancy, infants do not require nirsevimab unless they:

•    Meet medical criteria for increased risk of severe RSV disease (Box 1), OR
•    Were born <2 weeks after administration of RSVpreF vaccine.

The most frequent adverse effects of RSVpreF vaccine in pregnant persons were pain at injection site, headache, and myalgia^[5]. With regard to potential effects on the fetus, when RSVpreF was administered in pregnancy in clinical trials, receipt did not result in an increase in severe systemic adverse effects among infants compared with placebo. However, an imbalance was observed in preterm births between RSVpreF and placebo vaccine recipients^[5].

Figure 1. Summary of RSV prevention strategies (adapted from NACI statement)

 

CONCLUSION

RSV can cause severe respiratory disease requiring hospitalization in young infants and places a significant burden on the health care system. The development of new RSV vaccines and long-acting monoclonal antibodies offers promising prevention strategies that can significantly reduce the burden of RSV disease. However, the availability  of these preventive measures will vary across Canada because product purchasing and administration decisions are made at the provincial/territorial level.

Paediatricians and other HCPs have a crucial role in advocating for equitable access to RSV monoclonal  antibodies and vaccines. They should stay informed regarding available agents within their jurisdiction and counsel and support individual decisions that maximize protection against RSV. It is essential that children at the highest risk for severe RSV disease are prioritized, including those in northern, remote, and rural areas of Canada, where the potential health benefits and cost-effectiveness of these measures may be greatest. Until nirsevimab becomes part of preventive programming, provinces and territories should continue to offer palivizumab to infants at high risk of severe RSV disease.

CANADIAN PAEDIATRIC SOCIETY INFECTIOUS DISEASES AND IMMUNIZATION COMMITTEE (2024-2025)

Members: Michelle Barton MD (Chair), Laura Sauvé MD (Past Chair), Eugene Ng MD (Board Representative), Sean Bitnun MD, Sergio Fanella MD, Justin Penner MD, Jeannette Comeau MD MSc

Liaisons:  Dorothy L. Moore MD (National Advisory Committee on Immunization), Sean Bitnun MD (Canadian Paediatric and Perinatal HIV/AIDS Research Group), Isabelle Viel-Thériault MD (Committee to Advise on Tropical Medicine and Travel), Marina Salvadori MD (Public Health Agency of Canada), Sean O'Leary (American Academy of Pediatrics, Committee on Infectious Diseases), Rupeena Purewal MD (Immunization Monitoring Program, ACTive), Cora Constantinescu MD (Association of Medical Microbiology and Infectious Disease Canada, Pediatric Committee)

Principal authors: Jeannette L. Comeau MD MSc, Dorothy L. Moore MD, Michelle A. Barton MD

Potential Conflict of Interest
Dr Jeannette Comeau reported acting as a co-investigator on vaccine clinical trials (no direct financial compensation) for: GlaxoSmithKline Inc, ModernaTX Inc, Merck & Co. Inc, Sanofi Pasteur Inc, VBI Vaccines Inc, Pfizer, Medical R&D Inc, MedImmune LLC, and Janssen Research & Developement LLC. No other disclosures were reported.

Funding
There is no funding to declare.

---

References

---

Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.