Background

RSV is the dominant cause of severe lower respiratory tract infection (LRTI) in infants, with most severe disease concentrated in younger-age infants.

Methods

Healthy, pregnant women between 28 and 36 weeks gestation, with expected delivery near the start of the RSV season, were randomized to a single intramuscular dose of nanoparticle RSV F-protein vaccine, or placebo in a 2: 1 ratio. Their infants were followed for 180 days for medically-significant LRTI (MS-LRTI), LRTI with severe hypoxemia and/or LRTI-hospitalization. RSV detection was performed centrally by PCR. Safety evaluation continued until 364 days age.

Results

4,636 women were randomized, with 4,579 live births. Over the first 90 days of life, efficacy against RSV-MS-LRTI was 39.4%(97.52% CI:-1.0, 63.7%; p= 0.0278) and 41.4%(95% CI: 5.3, 61.2%) in the per protocol and expanded intent-to-treat (eITT) analyses, respectively. There was a lower rate (efficacy 58.8%; 95% CI 31.9, 75.0% in eITT analysis; not adjusted for multiplicity) of RSV-LRTI with severe hypoxemia in infants of vaccinees through 90 days age. Pneumonia reported as a serious adverse events was 49.4% less common in infants of vaccinees (2.6%) than placebo-recipients through 364 days age.

Conclusions

Maternal vaccination with RSV F-nanoparticle vaccine was safe and immunogenic. The prespecified primary endpoint success criterion (efficacy 97.5% lower bound≥ 30%) was not achieved. However, maternal immunization was associated with reduced risk of RSV-confirmed MS-LRTI and LRTI with severe hypoxemia in early infancy.