Efficacy and immunogenicity of a novel polyanhydride nanovaccine for use against RSV infection in the neonate

Abstract

Abstract Respiratory syncytial virus (RSV) is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Bovine RSV (BRSV) is closely related to human RSV and a significant cause of morbidity in young cattle. BRSV infection in calves displays many similarities to RSV infection in humans, including similar age dependency, gross and microscopic pathology, and innate and adaptive immune responses. The poor immunogenicity of RSV has been a complicating factor in the development of a safe and effective vaccine in both humans and calves. Polyanhydride nanovaccines (i.e. nanoparticle-based vaccines) have shown promise as adjuvants and vaccine delivery vehicles in rodent models due to their ability to promote enhanced immunogenicity through both the route of administration and the ability to provide sustained antigen exposure. In these studies, we determined the efficacy of a novel polyanhydride nanovaccine containing the stable, post-fusion F and G glycoproteins from BRSV, against RSV infection using a neonatal calf model. In vitro, the BRSV nanovaccine induced activation and cytokine secretion by monocyte-derived dendritic cells and alveolar macrophages. In vivo, calves receiving the BRSV F/G nanovaccine, followed by aerosol challenge with BRSV, demonstrated increased virus-specific IgA in the nasal and bronchoalveolar lavage fluid, an increase in RSV-specific cellular responses in the peripheral blood and airways, and a reduction in BRSV shedding compared to unvaccinated control calves. Our results suggest that the RSV-F/G nanovaccine is highly immunogenic and with optimization, has the potential to significantly reduce the disease burden associated with RSV infection in both humans and animals.