Moreover, recent evidence from human studies and experimentally corroborated by us4C6 suggested that the period just prior to delivery may be accompanied by a transient drop in immunity in pregnant females. of dams provides significant protection to pups from RSV challenge and reduced pulmonary inflammation. Collectively, our results show that a VLP vaccine with RSV F and G proteins is safe and effective for maternal and adult vaccination. Introduction Maternal vaccination against infections that affect mothers and infants is now routine and includes vaccines against influenza, tetanus, and pertussis. However, a maternal vaccine for respiratory syncytial virus (RSV) is not available in spite of a significant need. RSV is the single most important cause of acute viral respiratory disease in infants and young children frequently resulting in hospitalization of infants in the US and in significant mortality rates in developing countries1. Global RSV-associated acute lower respiratory infections in children under age 5 accounts for ~33 million cases annually with ~10% of them resulting in hospitalization and an in-hospital mortality rate of ~1C3%2. Maternal transfer of RSV immunity to infants is likely protective during the first Mouse monoclonal to CD95 months of life since the level of RSV immunity in mothers during the last trimester of pregnancy and the time of delivery correlates with levels of protection of infants3. Thus, increasing maternal RSV immunity during pregnancy could potentially extend the time of protection of their infants. Moreover, recent evidence from human studies and experimentally corroborated by us4C6 suggested that the period just prior to delivery may be accompanied by a transient drop in immunity in pregnant females. This finding suggests a window of vulnerability in pregnant mothers that may need to be considered during the rational design of RSV pirinixic acid (WY 14643) maternal vaccines. Thus, a maternal RSV vaccine that could benefit both mothers and infants would be desirable. A complication for development of a maternal RSV vaccine is that the vast majority of humans has experienced RSV infection by 2C5 years of age7. While naturally occurring pre-existing immunity is incompletely protective, it could well impact the effectiveness of a vaccine. Thus, a successful vaccine candidate must stimulate high titers of neutralizing antibody (NA) in the face of pre-existing immunity. Model animal systems using naive animals are instrumental in initial immunogenicity, safety, and efficacy vaccine studies, but may be suboptimal for directly mimicking human responses to RSV vaccines, which will virtually always be in the context of previous exposure(s). Use of live attenuated virus vaccines, which might overcome pre-existing immunity, are not recommended by regulatory entities to be used during pregnancy due to safety concerns. Virus-like particles (VLPs) are increasingly recognized as a safe and effective platform for developing vaccines against viral diseases8. VLPs are virus-sized particles composed of repeating structures on their surfaces and in their cores, structures that mimic those of infectious viruses, which contribute to VLPs immunogenicity. VLPs are formed by assembly of viral structural proteins and sometimes lipids into particles without the incorporation of the viral genome. Thus, VLPs are incapable of replication. The surface glycoproteins of enveloped viruses are folded and inserted into VLP membranes typical of an infectious virus, thereby retaining antigenic epitope conformation. We have recently described a Newcastle disease virus (NDV)-based VLP vaccine against RSV that stimulates safe and protective immune responses pirinixic acid (WY 14643) in mice and in cotton rats9,10. In addition, we have also demonstrated that cotton rats are a good model for testing the efficacy and safety of maternal vaccination against RSV6,11. Here we show the effect of previous RSV infection on induction of anti-RSV immunity by immunization with VLPs containing different conformational forms of the RSV F protein and the G protein in cotton rat females during gestation, and the ability?of these vaccines to provide protection from RSV challenge of offspring. VLP immunization significantly increases NA titers in both RSV-seropositive pregnant females and their litters. Importantly, litters of these animals are notably better safeguarded from RSV replication in the lungs than offspring of RSV naive, vaccinated animals. Furthermore, the transient immunosuppression in pregnant females soon before delivery is definitely prevented by pirinixic acid (WY 14643) VLP immunization. Pulmonary safety and serology in pups is definitely more robust in animals vaccinated with VLPs than animals vaccinated with purified F proteins. Pre-F protein-containing VLPs provide an immunologic advantage to dams and afford a moderate improvement in.