Based on this, enrolment was continued for a further Northern and Southern Hemisphere season. infants. Methods Healthy, pregnant women between 28 and 36 weeks gestation, with expected Sav1 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 Z-VAD-FMK 364 days age. Conclusions Maternal vaccination with RSV F-nanoparticle vaccine was safe and immunogenic. The prespecified main endpoint success criterion (efficacy 97.5% lesser bound 30%) was not achieved. However, maternal immunization Z-VAD-FMK was associated with reduced risk of RSV-confirmed MS-LRTI and LRTI with severe hypoxemia in early infancy. Z-VAD-FMK Trial Registration Number ClinicalTrials.Gov: “type”:”clinical-trial”,”attrs”:”text”:”NCT02624947″,”term_id”:”NCT02624947″NCT02624947. Funding statement Funded by Novavax, with supporting grant from your Bill and Melinda Gates Foundation. strong class=”kwd-title” Keywords: respiratory syncytial virus, efficacy, pregnancy, pneumonia, newborns, infants, phase III trial, immunogenicity, security, epidemiology, transplacental antibody transfer Z-VAD-FMK Background Respiratory syncytial computer virus (RSV) is the dominant cause of lower respiratory tract infection (LRTI)-related infant hospitalizations. In 2015, an estimated 3.2 million RSV-associated LRTI hospitalizations occurred worldwide, with 118,000 deaths in children under-5 years of age; 44% and 50% respectively in infants 6 months aged1. No licensed RSV vaccine exists, and timely active immunization against severe RSV disease in the first 3-6 months of life may be challenging. Passive immunity via transfer of IgG antibodies from immunized pregnant women offers an option, and is endorsed by the World Health Business for tetanus, influenza and pertussis prevention in infants2-4. Passive immunity conferred by palivizumab, a monoclonal antibody to RSV fusion (F) protein site-II epitope, reduces RSV-LRTI hospitalization in premature infants, and those with chronic lung disease or congenital heart disease5. Similarly, motavizumab (an experimental higher-potency palivizumab-like monoclonal antibody) reduced the risk for RSV LRTI hospitalization by 87% in Navajo infants given birth to at term6. Vaccination of pregnant women with recombinant RSV F-nanoparticle vaccine (RSV-F vaccine) was well-tolerated in a phase 2 trial, and elicited RSV A and B neutralizing antibodies, antibodies to RSV F-protein site-II epitope (palivizumab-competitive antibody, PCA), and other epitopes with broadly-neutralizing activity; and these were efficiently transferred to the infants7. We describe results of a Phase 3 trial evaluating the security and immunogenicity of RSV-F vaccine in pregnant women and vaccine efficacy (VE) against RSV-associated LRTI among their infants from birth through to 90-180 days of life. Methods Study design A randomized, observer-blind, placebo-controlled trial was undertaken at 87 sites in Argentina, Australia, Chile, Bangladesh, Mexico, New Zealand, Philippines, South Africa, Spain, United Kingdom and United States of America (USA). Healthy women 18 to 40 years Z-VAD-FMK aged with singleton pregnancies were injected between 280/7 and 366/7 weeks gestational age (GA), prior to anticipated blood circulation of.