Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, United States.
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, United States.
Elife. 2017 Dec 6;6:e30051. doi: 10.7554/eLife.30051.
Pathogens rely on proteins embedded on their surface to perform tasks essential for host infection. These obligatory structures exposed to the host immune system provide important targets for rational vaccine design. Here, we use a systematically designed series of multi-domain constructs in combination with small angle X-ray scattering (SAXS) to determine the structure of the main immunoreactive region from a major antigen from , LigB. An anti-LigB monoclonal antibody library exhibits cell binding and bactericidal activity with extensive domain coverage complementing the elongated architecture observed in the SAXS structure. Combining antigenic motifs in a single-domain chimeric immunoglobulin-like fold generated a vaccine that greatly enhances leptospiral protection over vaccination with single parent domains. Our study demonstrates how understanding an antigen's structure and antibody accessible surfaces can guide the design and engineering of improved recombinant antigen-based vaccines.
病原体依赖于其表面嵌入的蛋白质来执行宿主感染所必需的任务。这些暴露于宿主免疫系统的必需结构为合理的疫苗设计提供了重要的靶标。在这里，我们使用一系列经过系统设计的多结构域构建体，并结合小角度 X 射线散射（SAXS）来确定主要抗原 LigB 来自 的主要免疫反应区域的结构。抗 LigB 单克隆抗体文库表现出细胞结合和杀菌活性，具有广泛的结构域覆盖范围，补充了 SAXS 结构中观察到的伸长结构。将抗原表位组合在单个结构域嵌合免疫球蛋白样折叠中，产生的疫苗大大增强了钩端螺旋体的保护作用，超过了单个亲本结构域的疫苗接种效果。我们的研究表明，了解抗原的结构和抗体可及表面如何指导改进的基于重组抗原的疫苗的设计和工程。
