Genomics and Isolation Core

摘要 我们的STI CRC U19的目标是利用几十年的研究获得的知识来开发 有效的梅毒疫苗。开发梅毒疫苗的两个必要组成部分是i) 在循环病原体群体中鉴定选定疫苗候选的遗传变异 为疫苗开发提供信息，以及ii)分离最能反映遗传基因的现代梅毒菌株 可用于动物的循环病原菌的背景和毒力特征 在免疫试验之后的挑战。这些都是基因组学和隔离核心的目标。 在这个核心的三年活动中，我们将使用最近从梅毒中收集的生物样本- 感染患者提取和浓缩梅毒螺旋体DNA，并进行下一代全基因组 梅毒病原体数百个基因组的基因组测序。这类样本是从 地理上不同的位置，将提供对由此产生的抗原变异性的更深层次的理解 从编码我们选定的候选疫苗的基因的差异。此外，我们将分离出 生物样本(原发或继发皮损渗出物)中的现代梅毒螺旋体菌株 早期梅毒患者为动物挑战实验提供历史梅毒分离株的替代品。 我们将在基因组学和隔离核心中开展的工作将是这一计划的关键组成部分 在开发梅毒疫苗方面做出了杰出的努力。

ABSTRACT The goal of our STI CRC U19 is to use knowledge acquired over decades of research to develop an effective vaccine for syphilis. Two necessary components for the development of a syphilis vaccine are i) the identification of genetic variants for selected vaccine candidates in the circulating pathogen population to inform vaccine development, and ii) the isolation of modern syphilis strains, that best reflect the genetic background and virulence characteristics of circulating pathogens and that can be used for animal challenge following immunization experiments. These are the goals of the Genomics and Isolation Core. Over the three years of activity of this Core, we will use biological samples recently collected from syphilis- infected patients to extract and enrich for Treponema pallidum DNA, and perform next-generation whole genome sequencing of several hundred genomes of the syphilis agent. Such samples, collected from the geographically diverse locations, will provide a deeper understanding of the antigenic variability resulting from differences in the genes encoding our selected vaccine candidates. Additionally, we will isolate modern treponemal strains from biological samples (primary or secondary lesion exudates) collected from early syphilis patients to provide alternatives to historical syphilis isolates for animal challenge experiments. The work we will conduct in this Genomics and Isolation Core will be a critical component of this outstanding effort to develop a syphilis vaccine.