Abstract
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Maternal immunization is an option to increase maternal antibody levels and protect infants from infection. Here we assess the efficacy of virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations of the RSV F protein and the attachment RSV G protein in a maternal immunization model using cotton rats. VLP vaccines containing RSV F and G proteins strongly boost pre-existing RSV immunity in dams preventing their perinatal drop in immunity. Boosting is stronger for the pre-F VLP than for the post-F VLP or purified subunit F protein vaccines, giving an advantage on mothers’ protection. VLP immunization 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.
Highlights
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants
virus-like particle (VLP) used for immunization are based on Newcastle disease virus (NDV) core nucleocapsid (NP) and matrix (M) proteins and contain the ectodomain of the RSV G protein and the stabilized pre-fusion or post-fusion forms of the RSV F protein
The RSV F and G protein content and RSV F protein conformation in the two purified VLP preparations were quantified and characterized by western analysis and antibody binding to the purified VLPs (Supplementary Figs. 1–3)[9,13]
Summary
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. We assess the efficacy of virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations of the RSV F protein and the attachment RSV G protein in a maternal immunization model using cotton rats. VLP vaccines containing RSV F and G proteins strongly boost pre-existing RSV immunity in dams preventing their perinatal drop in immunity. Recent evidence from human studies and experimentally corroborated by us[4,5,6] 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 maternal vaccines. The surface glycoproteins of enveloped viruses are folded and inserted into VLP membranes typical of an infectious virus, thereby retaining antigenic epitope conformation
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