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钩端螺旋体通用分泌蛋白D(GspD),一种分泌素,可引发针对多种菌种和血清型的非补体依赖性杀菌抗体。

The Leptospiral General Secretory Protein D (GspD), a secretin, elicits complement-independent bactericidal antibody against diverse species and serovars.

作者信息

Schuler Eja, Marconi R T

机构信息

Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, 1112 E Clay St., Richmond, VA 23298, USA.

出版信息

Vaccine X. 2021 Feb 23;7:100089. doi: 10.1016/j.jvacx.2021.100089. eCollection 2021 Apr.

Abstract

Leptospirosis, the most common zoonotic infection worldwide, is a multi-system disorder affecting the kidney, liver, and lungs. Infections can be asymptomatic, self-limiting or progress to multi-organ system failure and pulmonary hemorrhage. The incidence of canine and human leptospirosis is steadily increasing worldwide. At least sixty-four species and several hundred lipopolysaccharide-based serovars have been defined. Preventive vaccines are available for use in veterinary medicine and limited use in humans in some countries. All commercially available vaccines are bacterin formulations that consist of a combination of laboratory cultivated strains of different lipopolysaccharide serotypes. The development of a broadly protective subunit vaccine would represent a significant step forward in efforts to combat leptospirosis in humans, livestock, and companion animals worldwide. Here we investigate the potential of General secretory protein D (GspD; LIC11570), a secretin, to serve as a possible antigen in a multi-valent vaccine formulation. GspD is conserved, expressed antigenic during infection and elicits antibody with complement independent bactericidal activity. Importantly, antibody to GspD is bactericidal against diverse species of the P1 subclade. Epitope mapping localized the bactericidal epitopes to the N-terminal N0 domain of GspD. The data within support further exploration of GspD as a candidate for inclusion in a next generation multi-protein subunit vaccine.

摘要

钩端螺旋体病是全球最常见的人畜共患感染病,是一种影响肾脏、肝脏和肺部的多系统疾病。感染可能无症状、自限性,或进展为多器官系统衰竭和肺出血。在全球范围内,犬类和人类钩端螺旋体病的发病率正在稳步上升。已确定至少64个物种和数百种基于脂多糖的血清型。预防性疫苗可用于兽医学,在一些国家也有限用于人类。所有市售疫苗均为菌苗制剂,由不同脂多糖血清型的实验室培养菌株组合而成。开发一种具有广泛保护作用的亚单位疫苗将是全球抗击人类、家畜和伴侣动物钩端螺旋体病努力中的重要一步。在此,我们研究了分泌素通用分泌蛋白D(GspD;LIC11570)作为多价疫苗制剂中可能抗原的潜力。GspD具有保守性,在感染期间表达抗原,并引发具有补体非依赖性杀菌活性的抗体。重要的是,针对GspD的抗体对P1亚分支的多种物种具有杀菌作用。表位作图将杀菌表位定位到GspD的N端N0结构域。这些数据支持进一步探索将GspD作为候选物纳入下一代多蛋白亚单位疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f85c/7941034/08eb01e2cac1/gr1.jpg

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