Earnhart Christopher G, Marconi Richard T
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia, USA.
Hum Vaccin. 2007 Nov-Dec;3(6):281-9. doi: 10.4161/hv.4661. Epub 2007 Jul 2.
Lyme disease is the most common vector-borne disease in North America and Europe and, if untreated, has significant arthritic, cardiac, dermatological and neurological sequelae. There is no currently available human Lyme disease vaccine. Outer surface protein C, because of its antigenicity, protective ability, and expression characteristics has emerged as a promising second generation vaccine candidate; however, significant sequence heterogeneity has impeded its development. Analyses of OspC sequences have revealed the existence of stable phylogenetic clusters or types, and that the type-defining sequence variation occurs within defined domains of the protein. Recent data indicating that immunodominant, and potentially protective OspC epitopes are located in these hypervariable regions has allowed development of a tetravalent, epitope-based, chimeric vaccine. In this report, we have extended that previously described tetravalent construct to include four additional OspC types. We demonstrate that the construct is highly immunogenic, and elicits type-specific antibodies that recognize each of the eight incorporated OspC type-specific epitopes. Antibody raised to the octavalent construct readily binds to the surface of strains expressing each component OspC type, indicating that the incorporated epitopes are presented on the surface of intact cells. In addition, the construct elicits antibody isotypes associated with complement-dependent bactericidal activity. These results represent an important step forward in the design of a broadly protective polyvalent OspC-based Lyme disease vaccine.
莱姆病是北美和欧洲最常见的媒介传播疾病，若不治疗，会引发严重的关节炎、心脏、皮肤和神经后遗症。目前尚无可用的人类莱姆病疫苗。外表面蛋白C因其抗原性、保护能力和表达特性，已成为一种有前景的第二代疫苗候选物；然而，显著的序列异质性阻碍了其开发。对OspC序列的分析揭示了稳定的系统发育簇或类型的存在，并且类型定义序列变异发生在该蛋白的特定结构域内。最近的数据表明，免疫显性且可能具有保护作用的OspC表位位于这些高变区，这使得基于表位的四价嵌合疫苗得以开发。在本报告中，我们扩展了先前描述的四价构建体，纳入了另外四种OspC类型。我们证明该构建体具有高度免疫原性，可引发识别八种并入的OspC类型特异性表位中每一种的类型特异性抗体。针对八价构建体产生的抗体能轻易结合表达每种组分OspC类型的菌株表面，表明并入的表位呈现在完整细胞表面。此外，该构建体引发与补体依赖性杀菌活性相关的抗体亚型。这些结果代表了在设计一种广泛保护性的基于OspC的多价莱姆病疫苗方面向前迈出的重要一步。
