Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 1680 Madison Avenue, Wooster, OH 44691, USA.
Vet Microbiol. 2013 Sep 27;166(1-2):47-58. doi: 10.1016/j.vetmic.2013.04.029. Epub 2013 May 20.
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.
猪繁殖与呼吸综合征(PRRS)是一种慢性猪病毒性疾病,一直对全球养猪业造成巨大的经济关注。在本研究中,我们开发了可生物降解的 PLGA [聚(D,L-丙交酯-co-乙交酯)]纳米颗粒包埋的灭活 PRRSV 疫苗(Nano-KAg),并经鼻腔给予猪一次,并评估了免疫相关性。在接受纳米-KAg 疫苗接种的同源病毒攻毒的猪中,在 2 周内观察到病毒血症完全清除,与未接种疫苗和灭活疫苗接种的猪相比,仅在肺部观察到病毒中和滴度显著增加。与对照组相比,纳米-KAg 疫苗接种猪的肺匀浆和血清中的 IFN-γ 水平更高,TGF-β 水平更低。来自纳米-KAg 疫苗接种猪肺部、血液、BAL 和 TBLN 的分离的单核细胞的再刺激分泌显著增加的 Th1 细胞因子 IFN-γ 和 IL-12。此外,在纳米-KAg 疫苗接种猪中观察到 CD3(+)CD8(+)、CD4(+)CD8(+)和 γδ T 细胞的频率更高,Foxp3(+)T 调节细胞的频率降低。因此,鼻内给予 Nano-KAg 疫苗可能是一种合适的策略,可以引发抗 PRRSV 免疫反应,从而更好地清除猪体内的病毒血症。