Vaccine Candidates Show Promise for Pediatric RSV

Drug Topics JournalDrug Topics December 2022
Volume 166
Issue 12

Results of multiple studies were presented at IDWeek 2022.

Two respiratory syncytial virus (RSV) prefusion F vaccine (RSVpreF) vaccines have shown promise as a potential prophylaxis for RSV in infants, according to research presented at during an oral abstract session1 at IDWeek 2022, held October 19 to 23 in Washington, D.C.

“It is not news to anybody in this room that RSV prevention in infants is an unmet medical need, with global hospitalizations in the millions each year, and approximately 150,000 deaths,” said Kimberly J. Center, MD, senior director, vaccine clinical research and development at Pfizer. “There is no widely available preventive measures, and no specific treatments for acute RSV illness.”

But because the concept of early-life disease protection through maternal antibodies is well-known and has been demonstrated in other viral and bacterial pathogens, this strategy is “attractive for RSV as well,” Center explained.

Investigators conducted a randomized, placebo-controlled phase 2b clinical trial2 (NCT04032093) evaluating safety, immunogenicity, and efficacy of the vaccine in women and their infants (n=579 and 572, respectively) across 4 countries. Between 24 and 36 weeks’ gestation, participants were randomly assigned to receive either 120 µg or 240 µg RSVpreF with or without aluminum hydroxide or placebo. The most common postvaccination reactions were injection site pain, fatigue, and myalgia, which were generally mild or moderate.

Any adverse events in either the month following vaccination or birth were anticipated events in pregnancy or the neonatal period; rates were similar between vaccine and placebo groups.

For all groups that received the vaccine, 50% neutralizing titers for both RSV-A and RSV-B rose “sharply” by the 2-week mark following vaccination. At delivery, geometric mean titer ratios for combined RSV-A/B were 10.9 to 13.6 in infants in both the maternal vaccine and placebo groups. Transplacental transfer ratios in all groups were 1.39 to 1.83, and through 6 months of life, geometric mean titer ratios were higher in infants whose mothers had received the vaccine vs placebo.

“Taken together, these findings established proof of concept for infant RSV lower respiratory tract infection prevention with a well-tolerated RSV prefusion F vaccine given across a broad range of gestational ages,” Center concluded.

In another RSV-focused abstract,3 Anastasia A. Aksyuk, PhD, director, translational medicine, vaccines & immune therapies, biopharmaceuticals R&D at AstraZeneca, presented data from a pooled analysis of two pivotal, placebo-controlled studies of nirsevimab, a potent monoclonal antibody to the RSV prefusion F protein with an extended half-life, for the prevention of lower respiratory tract infections in infants with RSV.

In 2 studies (MEDI8897 Ph2b, NCT02878330 and MELODY, NCT03979313), nirsevimab has demonstrated “consistent efficacy” in preventing medically-attended RSV lower respiratory tract infections through 150 days postvaccination, Aksyuk noted.

A cohort of healthy term and preterm infants were randomly assigned 2:1 to receive 1 intramuscular injection of nirsevimab or placebo before the infant’s first RSV season. Results of a pooled proposed dose analysis of both studies showed that no participant in either group with a medically attended RSV lower respiratory tract infection had an RSV isolate containing nirsevimab resistance-associated substitutions. Across treatment groups, participants with RSV isolates “harboring F protein sequence variations that maintained susceptibility to nirsevimab neutralization were balanced,” with no associations with RSV disease severity.

“We saw that nirsevimab neutralizes both RSV A and B subtypes,” Aksyuk concluded, adding that a lack of nirsevimab resistance after immunization supports the efficacy of this RSV vaccine.

Disclosures: Both presenters and multiple authors report financial relationships with industry. For details, see the full study abstracts.


  1. Schwenk H, Howard L. The news in viral infections in pediatrics. Presented at: IDWeek 2022; October 19-23, 2022; Washington, D.C. Oral Abstract session 33.
  2. Simões EAF, Madhi SA, Center KJ, et al. Establishing proof of concept for a bivalent RSVpreF subunit vaccine for maternal immunization. Presented at: IDWeek 2022; October 19-23, 2022; Washington, D.C. Poster 91.
  3. Abram ME, Ahani B, Tabor DE, et al. Pooled analysis of nirsevimab resistance through 150 days post dose in preterm and term infants. Presented at: IDWeek 2022; October 19-23, 2022; Washington, D.C. Poster 94.
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