Porcine reproductive and respiratory syndrome (PRRS) is a chronic viral disease of pigs, has been posing a huge economic concern to pig industry worldwide. In this study, we developed biodegradable PLGA [poly(d,l-lactide-co-glycolide)] nanoparticle-entrapped killed PRRSV vaccine (Nano-KAg), and administered intranasally to pigs once and evaluated the immune correlates. In Nano-KAg vaccinated homologous virus challenged pigs, complete clearance of viremia was observed in 2 weeks, associated with a significant increase in virus neutralizing titers only in the lungs, compared to both unvaccinated and killed vaccine vaccinated pigs. The lung homogenate and sera of Nano-KAg vaccinated pigs had higher levels of IFN-γ and lower levels of TGF-β than control groups. Restimulation of mononuclear cells isolated from the lungs, blood, BAL, and TBLN of Nano-KAg vaccinated pigs' secreted significantly increased levels of Th1 cytokines, IFN-γ and IL-12. In addition, higher frequencies of CD3(+)CD8(+), CD4(+)CD8(+), and γδ T cells, and reduced frequency of Foxp3(+) T-regulatory cells were observed in Nano-KAg vaccinated pigs. Thus, intranasal delivery of Nano-KAg vaccine may be a suitable strategy to elicit anti-PRRSV immune response required to better clear viremia in pigs.