Experimental Outer surface protein (Osp) C based subunit chimeritope vaccinogens for Lyme disease (LD) were assessed for immunogenicity, structure, ability to elicit antibody (Ab) responses to divergent OspC proteins, and bactericidal activity. Chimeritopes are chimeric epitope based proteins that consist of linear epitopes derived from multiple proteins or multiple variants of a protein. An inherent advantage to chimeritope vaccinogens is that they can be constructed to trigger broadly protective Ab responses. Three OspC chimeritope proteins were comparatively assessed: Chv1, Chv2 and Chv3. The Chv proteins possess the same set of 18 linear epitopes derived from 9 OspC type proteins but differ in the physical ordering of epitopes or by the presence or absence of linkers. All Chv proteins were immunogenic in mice and rats eliciting high titer Ab. Immunoblot and enzyme linked immunosorbent assays demonstrated that the Chv proteins elicit IgG that recognizes a diverse array of OspC type proteins. The panel included OspC proteins produced by N. American and European strains of the LD spirochetes. Rat anti-Chv antisera uniformly labeled intact, non-permeabilized Borreliella burgdorferi demonstrating that vaccinal Ab can bind to targets that are naturally presented on the spirochete cell surface. Vaccinal Ab also displayed potent complement dependent-Ab mediated killing activity. This study highlights the ability of OspC chimeritopes to serve as vaccinogens that trigger potentially broadly protective Ab responses. In addition to the current use of an OspC chimeritope in a canine LD vaccine, chimeritopes can serve as key components of human LD subunit vaccines.

中文翻译：

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莱姆病 OspC 嵌合体疫苗原的开发和优化。

评估了用于莱姆病 (LD) 的实验性外表面蛋白 (Osp) C 亚基嵌合体疫苗原的免疫原性、结构、引发对不同 OspC 蛋白的抗体 (Ab) 反应的能力以及杀菌活性。嵌合位是基于嵌合表位的蛋白质，其由源自多种蛋白质或蛋白质的多种变体的线性表位组成。嵌合体疫苗原的一个固有优势是它们可以被构建来触发广泛的保护性抗体反应。对三种 OspC 嵌合位蛋白进行了比较评估：Chv1、Chv2 和 Chv3。Chv 蛋白具有源自 9 个 OspC 型蛋白的相同组 18 个线性表位，但表位的物理顺序或接头的存在与否有所不同。所有 Chv 蛋白在小鼠和大鼠中均具有免疫原性，可引发高滴度抗体。免疫印迹和酶联免疫吸附测定表明，Chv 蛋白诱导 IgG 识别多种 OspC 型蛋白。该小组包括北美和欧洲 LD 螺旋体菌株产生的 OspC 蛋白。大鼠抗 Chv 抗血清均匀标记完整、非透化的伯氏疏螺旋体，证明疫苗抗体可以与螺旋体细胞表面天然存在的靶标结合。疫苗抗体还表现出有效的补体依赖性抗体介导的杀伤活性。这项研究强调了 OspC 嵌合位点作为疫苗原的能力，可触发潜在的广泛保护性抗体反应。除了目前在犬 LD 疫苗中使用 OspC 嵌合位外，嵌合位还可以作为人类 LD 亚单位疫苗的关键成分。