关键词: DNA vaccine LipL45 Th1 immune response electroporation leptospirosis

Mesh : Animals Antibodies, Bacterial / blood Bacterial Outer Membrane Proteins / genetics immunology Bacterial Vaccines / administration & dosage genetics immunology Electroporation Female Injections, Intramuscular Interferon-gamma / metabolism Interleukin-12 / metabolism Leptospirosis / prevention & control Leukocytes, Mononuclear / immunology Lipoproteins / genetics immunology Mice, Inbred BALB C Th1 Cells / immunology Vaccines, DNA / administration & dosage genetics immunology Vaccines, Synthetic / administration & dosage genetics immunology

来  源:   DOI:10.1080/21645515.2015.1047117   PDF(Sci-hub)

Abstract:
Leptospirosis is a bacterial zoonotic disease caused by an infection with a spirochete belonging to the genus Leptospira. In animals, leptospirosis displays a wide range of pathologies, including fever, abortion, icterus, and uveitis. Conversely, infection in humans is associated with multi-organ injury, resulting in an increased rate of fatalities. Pathogenic leptospires are able to translocate through cell monolayers at a rate significantly greater than that of non-pathogenic leptospires. Thus, vaccine approaches have been focused on targeting bacterial motility, lipopolysaccharides (LPSs), lipoproteins, outer-membrane proteins (OMPs) and other potential virulence factors. Previous studies have indicated that leptospiral proteins elicit long-lasting immunological memory in infected humans. In the study reported here, the efficacy of a synthetic consensus DNA vaccine developed against the Leptospira membrane lipoprotein LipL45 was tested. After in vivo electroporation (EP) mediated intramuscular immunization with a synthetic LipL45 DNA vaccine (pLipL45) immunized mice developed a significant cellular response along with the development of anti-LipL45-specific antibodies. Specifically, the pLipL45 vaccine induced a significant Th1 type immune response, indicated by the higher production of IL-12 and IFN-γ cytokines. The results presented here are the first demonstration that a LipL45 based DNA immunogen has potential as a anti-Leptospira vaccine.
摘要:
钩端螺旋体病是一种细菌性人畜共患疾病,由钩端螺旋体属螺旋体感染引起。在动物中,钩端螺旋体病表现出广泛的病理,包括发烧,流产,icterus,还有葡萄膜炎.相反,人类感染与多器官损伤有关,导致死亡率上升。致病性钩端螺旋体能够以明显高于非致病性钩端螺旋体的速率通过细胞单层易位。因此,疫苗方法一直专注于靶向细菌运动性,脂多糖(LPSs),脂蛋白,外膜蛋白(OMPs)和其他潜在的毒力因子。先前的研究表明,钩端螺旋体蛋白在受感染的人类中引起持久的免疫记忆。在这里报道的研究中,测试了针对钩端螺旋体膜脂蛋白LipL45开发的合成共有DNA疫苗的功效。在用合成的LipL45DNA疫苗(pLipL45)免疫的小鼠体内电穿孔(EP)介导的肌内免疫后,随着抗LipL45特异性抗体的产生,产生了显著的细胞应答。具体来说,pLipL45疫苗诱导了显著的Th1型免疫反应,IL-12和IFN-γ细胞因子的产量较高。这里呈现的结果是基于LipL45的DNA免疫原具有作为抗钩端螺旋体疫苗的潜力的首次证明。
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