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.

Background: The aim of the study was to investigate the effects of probiotics on moderate or severe atopic dermatitis (AD) in young children. Methods: Fifty six children aged 6-18 months with moderate or severe AD were recruited into a randomised double blind placebo controlled trial in Perth, Western Australia; 53 children completed the study. The children were given a probiotic (1610 9 Lactobacillus fermentum VRI-033 PCC; Probiomics) or an equivalent volume of placebo, twice daily for 8 weeks. A final assessment at 16 weeks was performed. Results: The main outcome measures were severity and extent of AD at the end of the study, as measured by the Severity Scoring of Atopic Dermatitis (SCORAD) index. The reduction in the SCORAD index over time was significant in the probiotic group (p = 0.03) but not the placebo group. Significantly more children receiving probiotics (n = 24, 92%) had a SCORAD index that was better than baseline at week 16 compared with the placebo group (n = 17, 63%) (p = 0.01). At the completion of the study more children in the probiotic group had mild AD (n = 14, 54%) compared to the placebo group (n = 8, 30%). Conclusion: Supplementation with probiotic L fermentum VRI-003 PCC is beneficial in improving the extent and severity of AD in young children with moderate or severe disease.

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