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针对白鼻综合征的病毒载体疫苗候选物可诱导小棕蝠(Myotis lucifugus)产生抗真菌免疫反应。

Virally-vectored vaccine candidates against white-nose syndrome induce anti-fungal immune response in little brown bats (Myotis lucifugus).

机构信息

US Geological Survey, National Wildlife Health Center, Madison, Wisconsin, USA.

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin - Madison, Madison, Wisconsin, USA.

出版信息

Sci Rep. 2019 May 1;9(1):6788. doi: 10.1038/s41598-019-43210-w.

Abstract

White-nose syndrome (WNS) caused by the fungus, Pseudogymnoascus destructans (Pd) has killed millions of North American hibernating bats. Currently, methods to prevent the disease are limited. We conducted two trials to assess potential WNS vaccine candidates in wild-caught Myotis lucifugus. In a pilot study, we immunized bats with one of four vaccine treatments or phosphate-buffered saline (PBS) as a control and challenged them with Pd upon transfer into hibernation chambers. Bats in one vaccine-treated group, that received raccoon poxviruses (RCN) expressing Pd calnexin (CAL) and serine protease (SP), developed WNS at a lower rate (1/10) than other treatments combined (14/23), although samples sizes were small. The results of a second similar trial provided additional support for this observation. Bats vaccinated orally or by injection with RCN-CAL and RCN-SP survived Pd challenge at a significantly higher rate (P = 0.01) than controls. Using RT-PCR and flow cytometry, combined with fluorescent in situ hybridization, we determined that expression of IFN-γ transcripts and the number of CD4 + T-helper cells transcribing this gene were elevated (P < 0.10) in stimulated lymphocytes from surviving vaccinees (n = 15) compared to controls (n = 3). We conclude that vaccination with virally-vectored Pd antigens induced antifungal immunity that could potentially protect bats against WNS.

摘要

由假球囊菌(Pseudogymnoascus destructans,Pd)引起的白鼻综合征(White-nose syndrome,WNS)已经导致了数百万只北美的冬眠蝙蝠死亡。目前,预防这种疾病的方法有限。我们进行了两项试验,以评估野生捕获的蝙蝠中潜在的 WNS 疫苗候选物。在一项试点研究中,我们用四种疫苗处理之一或磷酸盐缓冲盐水(phosphate-buffered saline,PBS)作为对照免疫蝙蝠,并在转移到冬眠室后用 Pd 对其进行挑战。在一个疫苗处理组中,接种表达 Pd 钙网蛋白(CAL)和丝氨酸蛋白酶(SP)的浣熊痘病毒(raccoon poxviruses,RCN)的蝙蝠,发病率(1/10)明显低于其他处理组(14/23),尽管样本量较小。第二次类似试验的结果为这一观察结果提供了更多支持。通过口服或注射 RCN-CAL 和 RCN-SP 接种疫苗的蝙蝠,在 Pd 挑战下的存活率(P = 0.01)明显高于对照组。通过 RT-PCR 和流式细胞术,结合荧光原位杂交,我们确定在幸存疫苗接种者(n = 15)的刺激淋巴细胞中,IFN-γ 转录物的表达和转录该基因的 CD4+辅助性 T 细胞的数量均升高(P < 0.10),与对照组(n = 3)相比。我们得出结论,用病毒载体的 Pd 抗原进行疫苗接种可以诱导抗真菌免疫,从而可能保护蝙蝠免受 WNS 的侵害。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/6494898/d29738e04722/41598_2019_43210_Fig1_HTML.jpg

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