背景:猪甲型流感病毒(swIAV)由于其高度传染性和急性病毒性疾病而成为养猪业的主要关注点。目前,大多数商业swIAV疫苗是传统的灭活病毒疫苗。基于植物乳杆菌的疫苗平台是粘膜疫苗开发的有希望的方法。口服和鼻内免疫有可能诱导粘膜免疫反应,赋予保护性免疫力。本研究的目的是评估三种植物乳杆菌菌株的益生菌潜力和粘附能力。此外,构建表达swIAV抗原HA1的头部结构域的重组植物乳杆菌菌株并评估其预防swIAV感染的能力。
结果:从健康猪粪便样品中分离的三种植物乳杆菌菌株在pH3和胆汁盐浓度为0.3%的条件下孵育时保持了最高的存活率。它们还显示出对肠道细胞的高粘附性。在活小鼠中监测所有三种植物乳杆菌菌株,并且没有观察到运输时间的主要差异。重组植物乳杆菌表达swIAVHA1蛋白(pSIP401-HA1-ZN-3)并赋予有效的粘膜,小鼠肠道以及上呼吸道的细胞和全身免疫反应。总之,植物乳杆菌菌株pSIP401-HA1-ZN-3在小鼠中口服和鼻内给药诱导粘膜免疫,最重要的是,提供针对致命流感病毒攻击的保护。
结论:总之,这些发现表明,工程植物乳杆菌菌株pSIP401-HA1-ZN-3可被视为在猪流感A大流行期间开发新型疫苗的替代方法。
BACKGROUND: Swine influenza A virus (swIAV) is a major concern for the swine industry owing to its highly contagious nature and acute viral disease. Currently, most commercial swIAV vaccines are traditional inactivated virus vaccines. The Lactobacillus plantarum-based vaccine platform is a promising approach for mucosal vaccine development. Oral and intranasal immunisations have the potential to induce a mucosal immune response, which confers protective immunity. The aim of this study was to evaluate the probiotic potential and adhesion ability of three L. plantarum strains. Furthermore, a recombinant L. plantarum strain expressing the head domain of swIAV antigen HA1 was constructed and evaluated for its ability to prevent swIAV infection.
RESULTS: The three L. plantarum strains isolated from healthy pig faecal samples maintained the highest survival rate when incubated at pH 3 and at bile salt concentration of 0.3%. They also showed high adherence to intestinal cells. All three L. plantarum strains were monitored in live mice, and no major differences in transit time were observed. Recombinant L. plantarum expressed swIAV HA1 protein (pSIP401-HA1-ZN-3) and conferred effective mucosal, cellular and systemic immune responses in the intestine as well as in the upper respiratory airways of mice. In conclusion, the oral and intranasal administration of L. plantarum strain pSIP401-HA1-ZN-3 in mice induced mucosal immunity and most importantly, provided protection against lethal influenza virus challenge.
CONCLUSIONS: In summary, these findings suggest that the engineered L. plantarum strain pSIP401-HA1-ZN-3 can be considered as an alternative approach for developing a novel vaccine during an swine influenza A pandemic.