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A single dose polyanhydride-based nanovaccine against paratuberculosis infection.
npj Vaccines ( IF 6.9 ) Pub Date : 2020-02-14 , DOI: 10.1038/s41541-020-0164-y
Akanksha Thukral 1 , Kathleen Ross 2, 3 , Chungyi Hansen 1 , Yashdeep Phanse 1, 3, 4 , Balaji Narasimhan 2, 3 , Howard Steinberg 1 , Adel M Talaat 1, 3, 4
Affiliation  

Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) 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 M. paratuberculosis. 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.

中文翻译:

一种抗副结核感染的单剂量聚酐纳米疫苗。

鸟分枝杆菌亚种。副结核病 (M. paratuberculosis) 在反刍动物中引起约内氏病,其特征是慢性胃肠炎,导致全球乳品业遭受重大经济损失。目前可用的疫苗(油基灭活菌苗)不能有效防止病原体脱落,很少用于控制奶牛群中的约内氏病。为了开发更好的疫苗来预防约内氏病的传播,我们利用聚酐纳米粒子 (PAN) 来封装由副结核分枝杆菌的全细胞裂解物 (PAN-Lysate) 和培养物滤液 (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)在小鼠中具有良好的耐受性,不会在注射部位引起炎症损伤。免疫学分析表明,PAN-Cf 疫苗接种组疫苗接种后抗原特异性 T 细胞反应水平显着增加,如产生 CD8+ T 的三重细胞因子(IFN-γ、IL-2、TNF-α)的高百分比所示细胞。攻击后,与接种灭活疫苗的动物相比,接种 PAN-Cf 的动物继续产生显着水平的双(IFN-γ、TNF-α)和单细胞因子(IFN-γ)分泌 CD8+T 细胞。在接种 PAN-Cf 的动物的多个器官中观察到细菌负荷显着减少,这是保护的明确指示。总体而言,聚酐纳米疫苗的使用导致针对约内氏病的保护性和持续免疫的发展,这种方法可用于对抗其他细胞内病原体。
更新日期:2020-02-14
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