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James Campbell, MD, MS, professor of pediatrics at University of Maryland School of Medicine and pediatrician at the University of Maryland Children's Hospital, recently gave a Grand Rounds presentation about a newly approved monoclonal antibody immunization method to protect against severe respiratory syncytial virus (RSV) in infants. The U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) recommends that all babies be given this immunization, called nirsevimab, before their first RSV season. In Grand Rounds, Dr. Campbell explained how the immunization works, its safety and efficacy, and the rationale for universal administration.

Background on RSV

RSV is an extraordinarily common virus that circulates widely, and 68 percent of babies in the United States will have had RSV by their first birthday. (Nearly all, 97 percent, will have had it by the time they turn two.) One-quarter of infants have lower respiratory-tract infections (LRTI) with RSV, which is a much higher percentage than in adults. RSV prevalence rates haven't changed significantly in the past two decades.

RSV is the number-one cause of hospitalization among infants in the U.S. Two to three percent of U.S. infants are hospitalized each year with RSV, with the highest hospitalization rates among babies younger than six months. One in five will need to go to the intensive care unit. Although premature babies are at higher risk, the majority – nearly 80 percent – of babies hospitalized with severe RSV have no other health problems.

There is a big opportunity to reduce public health burden and virtually eliminate severe RSV infections in infants with universal administration of nirsevimab.

Overview of RSV's virology

RSV is an orthopneumovirus, single-strand RNA, negative sense, with two cocirculating subtypes (A and B) and 11 proteins. Of those 11, the F and G proteins are the most important for vaccines and monoclonal antibodies.

What is the rationale for the recommendation of universal administration of nirsevimab?

Nirsevimab is a recombinant, neutralizing, fully human IgG1k long-acting monoclonal antibody. It provides passive immunization by binding to a highly conserved epitope on site 0 on the prefusion RSV protein F. It neutralizes both types of RSV (RSV A and RSV B) equally. Nirsevimab is more effective than the previous immunization product, palivizumab, because it binds to a better site on the virus. Nirsevimab was approved by the U.S. Food and Drug Administration (FDA) in July 2023, and in August 2023, ACIP made the following recommendations. Nirsevimab should be given to:

  • All infants under 8 months born during or entering first RSV season (in most places in the U.S. the administration window is October to March)
  • Infants 8 – 19 months who are at increased risk heading into RSV season 2

Why is nirsevimab universally recommended?

In the clinical trials presented to the FDA, nirsevimab was found to:

  • Reduce medically attended RSV LRTI by 79%
  • Reduce RSV LRTI hospitalization by 80%
  • Reduce RSV LRTI ICU admission by 90%

A large-scale, real-world study of more than 8,000 infants in France, the UK, and Germany confirmed these results in real-world conditions. (The results of this study, called the HARMONIE trial, have been published in the New England Journal of Medicine). The study found that nirsevimab:

  • Reduced severe RSV disease by 76%
  • Reduced hospitalization for RSV by 83%
  • Did not present any significant safety concerns

What is nirsevimab's potential, and what barriers remain to universal administration?

As we did with the rotavirus vaccine in the U.S., we could reduce the public health burden significantly by distributing the RSV vaccine to every young child. Statistically speaking, vaccinating 128 infants with nirsevimab prevents one hospitalization from RSV. Comparing that to other viruses, we'd need to vaccinate 2,000 infants against influenza to prevent a flu-related hospitalization.

Hurdles to universal administration include:

  • The immunization's expense ($495 in the private sector, $395 in the public sector) – we have established a mechanism to ensure equitable access by inclusion of this product in the Vaccines For Children program
  • The complexity of sharing information about whether the child's mother got the RSV vaccine while pregnant or whether the child got the RSV immunization in the hospital, to inform care in the outpatient setting pediatrician's office
  • Having enough doses to meet the demand

These hurdles can, and should, be overcome, to reduce this disease's toll on our country's youngest residents.

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