PDF(Pubmed)
Abstract：
Porcine epidemic diarrhea virus (PEDV) causes acute watery diarrhea and high mortality in newborn piglets. Activation of intestinal mucosal immunity is crucial to anti-PEDV infection. To develop a vaccine capable of stimulating intestinal mucosal immunity, we prepared a bacterium (Lactococcus lactis)-like particle (BLP) vaccine (S1-BLPs) displaying the S1 protein, a domain of PEDV spike protein (S), based on gram-positive enhancer matrix (GEM) particle display technology. We further compared the effects of different vaccination routes on mucosal immune responses in mice induced by S1-BLPs. The specific IgG titer in serum of intramuscularly immunized mice with S1-BLPs was significantly higher than that of the intranasally administered. The specific IgA antibody was found in the serum and intestinal lavage fluid of mice vaccinated intranasally, but not intramuscularly. Moreover, the intranasally inoculated S1-BLPs induced higher levels of IFN-γ and IL-4 in serum than the intramuscularly inoculated. In addition, the ratio of serum IgG2a/IgG1 of mice inoculated intramuscularly was significantly higher with S1-BLPs compared to that of with S1 protein, suggesting that the immune responses induced by S1-BLPs was characterized by helper T (Th) cell type 1 immunity. The results indicated that S1-BLPs induced systemic and local immunity, and the immunization routes significantly affected the specific antibody classes and Th immune response types. The intranasally administered S1-BLPs could effectively stimulate intestinal mucosal specific secretory IgA response. S1-BLPs have the potential to be developed as PEDV mucosal vaccine.
摘要：
猪流行性腹泻病毒(PEDV)引起新生仔猪急性水样腹泻和高死亡率。肠道粘膜免疫的激活对于抗PEDV感染至关重要。为了开发能够刺激肠道粘膜免疫的疫苗，我们制备了一种显示S1蛋白的细菌（乳酸乳球菌）样颗粒（BLP）疫苗（S1-BLPs），PEDV刺突蛋白（S）的一个结构域，基于革兰氏阳性增强剂矩阵(GEM)粒子显示技术。我们进一步比较了不同接种途径对S1-BLP诱导的小鼠粘膜免疫应答的影响。S1-BLP肌内免疫小鼠血清中的特异性IgG滴度明显高于鼻内给药。在小鼠血清和肠道灌洗液中发现特异性IgA抗体。但不是肌肉内.此外，鼻内接种的S1-BLP诱导血清中的IFN-γ和IL-4水平高于肌内接种。此外,与S1蛋白相比，肌内接种S1-BLPs的小鼠血清IgG2a/IgG1的比值明显更高，提示S1-BLPs诱导的免疫应答以辅助性T（Th）细胞1型免疫为特征。结果表明，S1-BLPs诱导全身和局部免疫，免疫途径显著影响特异性抗体类别和Th免疫应答类型。鼻内给药S1-BLP可以有效刺激肠粘膜特异性分泌IgA反应。S1-BLPs具有开发PEDV粘膜疫苗的潜力。
