Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants

Abstract

Summary of study A multi-country randomized, placebo-controlled trial of the safety, immunogenicity and efficacy of respiratory syncytial virus (RSV) F-protein nanoparticle vaccine was undertaken in 4,636 pregnant women and their infants. RSV F-protein vaccine was safe and immunogenic in the pregnant women inducing anti-F IgG, palivizumab-competing antibodies and RSV neutralizing antibodies that were transferred to the fetus. Although the primary endpoint of prevention of RSV-specific medically-significant lower respiratory tract infection (MS-LRTI) was not met per protocol criteria for efficacy (i.e. 97.52% lower bound >30%), vaccine efficacy was 39.4% (97.52% CI: -1.0, 63.7%; p=0.0278) in infants 0-90 days age. Furthermore, there was a 58.8% (95% CI 31.9, 75.0%) lower rate of RSV LRTI with severe hypoxemia (secondary endpoint) through to 90 days of age in the expanded intent-to-treat analysis. The number of women needed to be vaccinated to prevent RSV-specific MS-LRTI or LRTI with severe hypoxemia in their infants through to 180 days of life were 88 and 82, respectively. 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. Trial Registration Number ClinicalTrials.Gov: NCT02624947. Funding statement Funded by Novavax, with supporting grant from the Bill and Melinda Gates Foundation.

A guide to vaccinology: from basic principles to new developments

“…Maternal vaccination with pertussis 24 , tetanus 25 and influenza 26 vaccines harnesses this important protective adaptation to reduce the risk of disease soon after birth and clearly demonstrates the role of antibodies in protection against these diseases. Vaccination of pregnant women against group B streptococci 27 and respiratory syncytial virus (RSV) 28 has not yet been shown to be effective at preventing neonatal or infant infection, but it has the potential to reduce the burden of disease in the youngest infants. Other examples include the use of specific neutralizing antibodies purified from immune donors to prevent the transmission of various viruses, including varicella zoster virus, HBV and measles virus 29 .…”

Flexible modelling of risk factors on the incidence of pneumonia in young children in South Africa using piece-wise exponential additive mixed modelling

“…Rudan et al [ 10 ] and Janet et al [ 31 ] highlight that the peak incidence of respiratory syncytial virus occurs for a period of 2 – 4 months during the cold seasons. Respiratory syncytial virus is the leading viral cause of hospitalized pneumonia in children who are immunised with PCV and HiB [ 32 ]. Further research is needed to study this association in the DCHS birth cohort.…”

Coronavirus disease 2019 vaccines in pregnancy

“… 20 , 21 Novel vaccines have been studied in pregnant women both during a pandemic situation, such as H1N1 influenza, 22 and outside a pandemic, such as recent trials of respiratory syncytial virus and group B streptococcus vaccines. 23 , 24 Although there are reported plans to enroll pregnant women following the completion of phase 3 trials, no manufacturer has publicly released their timeline for the initiation of such studies.…”