Respiratory syncytial virus (RSV) is a negative-sense, single-stranded, ribonucleic acid (RNA) virus that is a member of Pneumoviridae family. Two subtypes, A and B, and multiple genotypes circulate during fall and winter seasonal outbreaks of RSV.1 RSV can cause severe lower respiratory tract disease including bronchiolitis, pneumonia, respiratory failure, and death. Each year, RSV disease causes the hospitalization of 1.5% to 2% of children younger than 6 months of age, resulting in 100 to 300 deaths.2 For infants younger than 1 year, RSV infection is the leading cause of hospitalization.3 In 2023, two new treatments have become available to prevent RSV disease: nirsevimab and RSVPreF vaccine.
Nirsevimab
Nirsevimab is an antibody to an RSV antigen. It has a long half-life and is approved for administration to infants, providing passive immunization. In contrast, administration of the RSVPreF vaccine to pregnant persons elicits active maternal immunity, resulting in the production of anti-RSV antibodies that are transferred to the fetus, resulting in passive immunity in the infant. Seasonal administration of nirsevimab and the RSV vaccine maximizes benefit to the infant and conserves limited health care resources. In temperate regions in the United States, the RSV infection season typically begins in October and peaks in December through mid-February and ends in April or May.4,5 In southern Florida, the RSV season often begins in August to September, peaks in November through December, and ends in March.4,5
This editorial reviews 3 strategies for prevention of RSV infection in infants, including:
- universal treatment of newborns with nirsevimab
- immunization of pregnant persons with an RSVpreF vaccine in the third trimester appropriately timed to occur just before the beginning or during RSV infection season
- prioritizing universal maternal RSV vaccination with reflex administration of nirsevimab to newborns when the pregnant person was not vaccinated.6
Of note, there are no studies that have evaluated the effectiveness of combining RSVpreF vaccine and nirsevimab. The Centers for Disease Control and Prevention (CDC) does not recommend combining both RSV vaccination of pregnant persons plus nirsevimab treatment of the infant, except in limited circumstances, such as for immunocompromised pregnant people with limited antibody production or newborns who have a massive transfusion, which dilutes antibody titres.6
RSV prevention strategy 1
Universal treatment of newborns and infants with nirsevimab
Nirsevimab (Beyfortus, Sanofi and AstraZeneca) is an IgG 1-kappa monoclonal antibody with a long half-life that targets the prefusion conformation of the RSV F-protein, resulting in passive immunity to infection.7 Passive immunization results in rapid protection against infection because it does not require activation of the immune system. Nirsevimab is long acting due to amino acid substitutions in the Fc region, increasing binding to the neonatal Fc receptor, which protects IgG antibodies from degradation, thereby extending the antibody half-life. The terminal halflife of nirsevimab is 71 days, and the duration of protection following a single dose is at least 5 months.
Nirsevimab is approved by the US Food and Drug Administration (FDA) for all neonates and infants born or entering their first RSV infection season and for children up to 24 months of age who are vulnerable to severe RSV during their second RSV infection season. For infants born outside the RSV infection season, nirsevimab should be administered once prior to the start of the next RSV infection season.7 Nirsevimab is administered as a single intramuscular injection at a dose of 50 mg for neonates and infants < 5 kg in weight and a dose of 100 mg for neonates and infants ≥ 5 kg in weight.7 The list average wholesale price for both doses is $594.8 Nirsevimab is contraindicated for patients with a serious hypersensitivity reaction to nirsevimab or its excipients.7 In clinical trials, adverse reactions including rash and injection site reaction were reported in 1.2% of participants.7 Some RSV variants may be resistant to neutralization with nirsevimab.7,9
In a randomized clinical trial, 1,490 infants born ≥ 35 weeks’ gestation, the rates of medically-attended RSV lower respiratory tract disease (MA RSV LRTD) through 150 days of follow-up in the placebo and nirsevimab groups were 5.0% and 1.2%, respectively (P < .001).7,10 Compared with placebo, nirsevimab reduced hospitalizations due to RSV LRTD by 60% through 150 days of follow up. In a randomized clinical trial enrolling 1,453 infants born between 29 weeks’ and < 35 weeks’ gestation, the rates of MA RSV LRTD through 150 days of follow up in the placebo and nirsevimab groups were 9.5% and 2.6%, respectively (P < .001). In this study of infants born preterm, compared with placebo, nirsevimab reduced hospitalization due to RSV LRTD by 70% through 150 days of follow up.7 Nirsevimab is thought to be cost-effective at the current price per dose, but more data are needed to precisely define the magnitude of the health care savings associated with universal nirsevimab administration.11-13 The CDC reports that the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) of nirsevimab administration to infants is approximately $250,000, given an estimated cost of $500 for one dose of vaccine.14
Universal passive vaccination of newborns is recommended by many state departments of public health, which can provide the vaccine without cost to clinicians and health care facilities participating in the children’s vaccination program.
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