#09-213

Complete

Date Full Report Received

11/29/2011

Date Abstract Report Received

11/29/2011

Investigation

Institution:
Primary Investigator:

Porcine Reproductive and Respiratory Syndrome (PRRS) is an economically important chronic viral disease of pigs. Available PRRS virus (PRRSV) vaccines are not completely protective to control the disease outbreaks. Conventional PRRSV vaccines administered by intramuscular injection reduced the persistence and duration of viral shedding, but failed to eliminate the wild-type homologous virus. Most importantly, the vaccines failed to prevent re-infections and infection caused by heterologous PRRSV. It is known that successful activation of mucosal immune cells by intranasal immunization provides both local mucosal and systemic immunity to effectively control respiratory viral infections. Aim of this project was to evaluate mucosal adjuvanticity of adjuvants, cholera toxin and OK432 (Streptoccocus pyogenes product) to boost modified live PRRSV vaccine (MLV-PRRS) administered intranasally to pigs. Other aim is to evaluate PRRSV killed vaccine delivery system by a nanotechnology based approach to generate protective mucosal immunity to PRRS. Our results suggested that cholera toxin B subunit and OK432 upregulated the anti-PRRSV specific immune response to MLV-PRRS to both homologous and heterologous PRRSV challenge. But unlike the adjuvant Mycobacterium tuberculosis whole cell lysate (M. tb WCL) these two adjuvants failed to suppress the immunosuppressive responses induced by PRRSV. Our research on development of a killed PRRSV vaccine by entrapping PRRSV killed vaccine in nanoparticles prepared using poly DL-lactide-co-glycolide (PLGA) (nanoparticle-killed-PRRSV vaccine) was successful, and we detected internalization and stimulation of alveolar macrophages by the candidate vaccine in vitro. Our in vivo results suggested that intranasally administered nanoparticle-killed-PRRSV vaccine is capable of inducing protective immune responses, associated with absence of clinical PRRS and significantly reduced viremia and the viral load in the challenged pigs. We conclude that protective anti-PRRSV mucosal immunity is critical to control PRRSV outbreaks and that could be achieved when PRRSV vaccines are administered by intranasal route using suitable potent adjuvants and delivery system.