High-throughput Epitope Mapping of Anti-Viral Antibodies

描述(申请人提供)：从感染HIV-1的捐赠者中分离出的高效力和广谱中和抗体的鉴定表明，当呈现合适的抗原结构时，人类免疫系统可以产生HIV-1无法逃避的保护性抗体。了解这些抗原结构是开发能够产生广泛保护性体液免疫的疫苗的主要目标。大多数这些广泛中和的单抗结合在包膜上的构象复杂的表位，这些表位很难进行表位映射，越来越多的这样的单抗正在被用更有效的方法来分离鉴定。然而，表征单抗的能力并没有跟上，在分离相关单抗的日益增长的能力和从分子上定义产生它们的免疫原性结构的能力之间留下了很大的差距。这项建议的目标是开发工具，以快速和全面地映射结构复杂的病毒包膜蛋白上的单抗表位。识别有效和广泛中和的单抗的表位，将使表现出改进的抗原特性的环境变异体能够更快地作为候选疫苗进行设计和测试。 公共卫生相关性：该项目将通过确定有效和广泛中和的单抗的表位来促进人类健康，以便能够更快地设计和测试具有改进的抗原特性的环境变异体作为候选疫苗。

DESCRIPTION (provided by applicant): The identification of highly potent and broadly neutralizing antibodies isolated from HIV-1- infected donors suggests that when presented with a suitable antigenic structure, the human immune system can produce protective antibodies that HIV-1 is unable to evade. Understanding these antigenic structures is a primary objective in developing a vaccine capable of generating broadly protective humoral immunity. Most of these broadly neutralizing MAbs bind conformationally complex epitopes on Envelope that have been difficult to epitope map, and an increasing number of such MAbs are being identified using more efficient approaches to MAb isolation. However, the ability to characterize MAbs has not kept up, leaving a major gap between the growing ability to isolate relevant MAbs and the ability to molecularly define the immunogenic structures that gave rise to them. The goal of this proposal is to develop tools to rapidly and comprehensively map MAb epitopes on structurally complex viral Envelope proteins. Identifying the epitopes of potent and broadly neutralizing MAbs will enable Env variants exhibiting improved antigenic characteristics to be more rapidly designed and tested as vaccine candidates. PUBLIC HEALTH RELEVANCE: This project will contribute to human health by identifying the epitopes of potent and broadly neutralizing MAbs so that Env variants exhibiting improved antigenic characteristics can be more rapidly designed and tested as vaccine candidates.