Mucosal immunization with an attenuated Salmonella vaccine partially protects white-tailed deer from chronic wasting disease
Mucosal immunization with an attenuated Salmonella vaccine partially protects white-tailed deer from chronic wasting disease
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DOI：
10.1016/j.vaccine.2014.11.035
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发表时间：
2015-01-25
期刊：
影响因子：
5.5
通讯作者：
Wisniewski, Thomas
中科院分区：
文献类型：
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作者：
Goni, Fernando;Mathiason, Candace K.;Wisniewski, Thomas
朊病毒病是一类独特的疾病，影响动物和人类，其潜在发病机制与称为 PrPC（C 代表细胞）的正常自身蛋白向称为 PrPSc（Sc 代表瘙痒病）的病理性和传染性构象异构体的构象变化有关。牛海绵状脑病（BSE）是一种朊病毒疾病，据信是由于用受朊病毒污染的肉和骨粉产品喂养牛而引起的，它跨越物种障碍感染人类。慢性消耗性疾病（CWD）感染大量鹿和麋鹿，并有可能感染人类。目前朊病毒病尚无有效的治疗方法。此前，我们已经证明，我们可以通过粘膜疫苗预防部分易感小鼠体内朊病毒的传播。在当前的研究中，白尾鹿口服接种了表达 PrP 的减毒沙门氏菌，而对照鹿则口服了载体减毒沙门氏菌。一旦建立了粘膜反应，就通过在扁桃体和直肠粘膜上施用聚合重组PrP来口服和局部加强接种疫苗的动物。然后用 CVVD 感染的脑匀浆口服攻击接种疫苗的动物和对照动物。 CWD口服攻击三年后，所有对照鹿均出现临床CWD（中位生存期602天），而在接种疫苗的鹿中，潜伏期显着延长（中位生存期909天；威布尔回归分析p = 0.012），并且一只鹿在临床上以及RAMALT和扁桃体活检中均未出现CWD。这种阴性疫苗在唾液中具有最高滴度的 IgA 和针对 PrP 的全身 IgG。蛋白质印迹显示该疫苗中的免疫球蛋白与 PrPCWD 发生反应。我们记录了在自然面临风险的物种中首次部分成功地接种朊病毒病疫苗。 (C) 2014 Elsevier Ltd. 保留所有权利。
Prion disease is a unique category of illness, affecting both animals and humans, in which the underlying pathogenesis is related to a conformational change of a normal, self-protein called PrPC (C for cellular) to a pathological and infectious conformer known as PrPSc (Sc for scrapie). Bovine spongiform encephalopathy (BSE), a prion disease believed to have arisen from feeding cattle with prion contaminated meat and bone meal products, crossed the species barrier to infect humans. Chronic wasting disease (CWD) infects large numbers of deer and elk, with the potential to infect humans. Currently no prionosis has an effective treatment. Previously, we have demonstrated we could prevent transmission of prions in a proportion of susceptible mice with a mucosal vaccine. In the current study, white-tailed deer were orally inoculated with attenuated Salmonella expressing PrP, while control deer were orally inoculated with vehicle attenuated Salmonella. Once a mucosal response was established, the vaccinated animals were boosted orally and locally by application of polymerized recombinant PrP onto the tonsils and rectal mucosa. The vaccinated and control animals were then challenged orally with CVVD-infected brain homogenate. Three years post CWD oral challenge all control deer developed clinical CWD (median survival 602 days), while among the vaccinated there was a significant prolongation of the incubation period (median survival 909 days; p = 0.012 by Weibull regression analysis) and one deer has remained CWD free both clinically and by RAMALT and tonsil biopsies. This negative vaccinate has the highest titers of IgA in saliva and systemic IgG against PrP. Western blots showed that immunoglobulins from this vaccinate react to PrPCWD. We document the first partially successful vaccination for a prion disease in a species naturally at risk. (C) 2014 Elsevier Ltd. All rights reserved.