DEVELOPMENT OF A NANOPARTICULATE VACCINE AGAINST INFECTIOUS DISEASES IN PIG INDUSTRY

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that continues to cause significant economic losses to the swine industry worldwide. Inactivated and live-attenuated vaccines provide limited cross-protection and short-lived immunity. The mainstay of PEDV control is immunization of breeding herds with subunit vaccines based on the PEDV spike (S) protein. The poor immunogenicity of PEDV subunit vaccines coupled with the reproductive toxicity of traditional oil-based adjuvants, has limited their application in breeding herds. This dissertation presents the development and optimization of a new biodegradable nanoparticle (NP)-based vaccine platform that can induce protective immunity against PEDV while being safe for reproduction.The poly(lactic-co-glycolic acid) (PLGA) was used to formulate a delivery system for PEDV spike antigen and the selected oil-based immunostimulatory adjuvants. Nanoparticle formulations were prepared using a double-emulsion solvent evaporation method. Variables such as polymer composition, stabilizer concentrations, phase ratios, and sonication parameters were systematically evaluated to optimize NP fabrication. Physicochemical characterization revealed that the antigen was stable and maintained its integrity during processing and storage. In vitro release studies showed a biphasic release pattern, with an initial release of 0.65 ± 0.04 µg (followed by a sustained release of vaccine components over 14 days). The release kinetics provides prolonged exposure and may reduce the need for boosters. Freeze-drying studies also demonstrated that the developed nanoparticles (NPs) are amenable to lyophilization and remain physiochemically stable in dry powder form, making them suitable for large-scale manufacturing and distribution. In vivo studies, conducted in collaboration with Dr. Heather Wilson’s laboratory, confirmed that the optimized NP vaccine is safe when delivered either intramuscularly or intrauterinely to breeding gilts. The formulation also elicited robust antigen-specific immune responses and was not detrimental to fertility or reproductive performance. The results show that the PLGA-based vaccine platform provides a practical solution that balances safety, stability, and immunogenicity for use in commercial swine operations. In conclusion, this dissertation describes the development of a new generation of PEDV subunit vaccine using PLGA NPs that provides safety, stability, and potent immune activation. The vaccine formulation overcomes major limitations of PEDV vaccines currently in use, specifically reproductive toxicity and poor mucosal immunity. In addition to PEDV, this platform can serve as a foundation for development of next-generation nanovaccines against other viral pathogens of veterinary and human health.