(603d) Mucosal Polyanhydride Nanovaccine Against Respiratory Syncytial Virus Infection in the Neonatal Calf
Polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) represent a safe and efficacious platform technology with the capability to enhance immune responses against pathogens such as BRSV. These materials are biocompatible, providing mild inflammation at the injection site. Due to their hydrophobic properties, they provide sustained release of encapsulated proteins, which allows for dose sparing, and display chemistry-dependent internalization and activation by antigen presenting cells, which allows for the ability to modulate immune responses. In the current study, the efficacy of a polyanhydride nanovaccine encapsulating the BRSV F and G glycoproteins was evaluated in the neonatal calf. The nanovaccine released immunologically active antigen, evidenced by the ability of BRSV immune serum to bind the released proteins, as well as stimulate CD4+ T cells from BRSV-immune cows. The nanovaccine demonstrated the ability to activate bovine monocyte-derived dendritic cells and alveolar macrophages through the secretion of IFN-Æ, TNF-Î±, IL-6, and IL-1Î². Following intranasal administration to calves, the nanovaccine allowed for reduced gross pathology and histopathology in the lungs as well as viral burden in the lungs. Nasal fluid and bronchoalveolar lavage fluid showed statistically significantly higher levels of IgA compared to unvaccinated controls, as well as higher viral neutralization titer six days post-challenge. Peripheral blood mononuclear cells from the nanovaccine-immunized calves stimulated with the F and G proteins demonstrated enhanced T cell responses compared to unvaccinated calves, with a significantly higher degree of dividing T cells, as well as secreted IFN-Æ and IL-17. These results demonstrate that a single intranasal dose of a polyanhydride nanovaccine encapsulating the BRSV F and G glycoproteins was an effective vaccine platform that allowed for robust adaptive immune responses against BRSV.