Thukral Akanksha, Ross Kathleen, Hansen Chungyi, Phanse Yashdeep, Narasimhan Balaji, Steinberg Howard, Talaat Adel M
1Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706 USA.
2Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50010 USA.
NPJ Vaccines. 2020 Feb 14;5(1):15. doi: 10.1038/s41541-020-0164-y. eCollection 2020.
subsp () causes Johne's disease in ruminants and is characterized by chronic gastroenteritis leading to heavy economic losses to the dairy industry worldwide. The currently available vaccine (inactivated bacterin in oil base) is not effective in preventing pathogen shedding and is rarely used to control Johne's disease in dairy herds. To develop a better vaccine that can prevent the spread of Johne's disease, we utilized polyanhydride nanoparticles (PAN) to encapsulate mycobacterial antigens composed of whole cell lysate (PAN-Lysate) and culture filtrate (PAN-Cf) of . These nanoparticle-based vaccines (i.e., nanovaccines) were well tolerated in mice causing no inflammatory lesions at the site of injection. Immunological assays demonstrated a substantial increase in the levels of antigen-specific T cell responses post-vaccination in the PAN-Cf vaccinated group as indicated by high percentages of triple cytokine (IFN-γ, IL-2, TNF-α) producing CD8 T cells. Following challenge, animals vaccinated with PAN-Cf continued to produce significant levels of double (IFN-γ, TNF-α) and single cytokine (IFN-γ) secreting CD8 T cells compared with animals vaccinated with an inactivated vaccine. A significant reduction in bacterial load was observed in multiple organs of animals vaccinated with PAN-Cf, which is a clear indication of protection. Overall, the use of polyanhydride nanovaccines resulted in development of protective and sustained immunity against Johne's disease, an approach that could be applied to counter other intracellular pathogens.
副结核分枝杆菌（subsp ()）可引起反刍动物的副结核病，其特征为慢性肠胃炎，给全球乳制品行业造成巨大经济损失。目前可用的疫苗（油佐剂灭活菌苗）在预防病原体传播方面效果不佳，很少用于控制奶牛群中的副结核病。为开发一种能更好预防副结核病传播的疫苗，我们利用聚酸酐纳米颗粒（PAN）包裹由副结核分枝杆菌的全细胞裂解物（PAN - 裂解物）和培养滤液（PAN - Cf）组成的分枝杆菌抗原。这些基于纳米颗粒的疫苗（即纳米疫苗）在小鼠中耐受性良好，注射部位未出现炎症病变。免疫测定表明，接种PAN - Cf疫苗组在接种后抗原特异性T细胞反应水平大幅增加，这表现为产生三重细胞因子（IFN - γ、IL - 2、TNF - α）的CD8 T细胞百分比很高。在攻毒后，与接种灭活疫苗的动物相比，接种PAN - Cf的动物持续产生大量分泌双重细胞因子（IFN - γ、TNF - α）和单一细胞因子（IFN - γ）的CD8 T细胞。在接种PAN - Cf的动物的多个器官中观察到细菌载量显著降低，这是保护作用的明确迹象。总体而言，聚酸酐纳米疫苗的使用导致对副结核病产生保护性和持续性免疫，这一方法可应用于对抗其他细胞内病原体。
