Genomics and Isolation Core

摘要 我们的STI CRC U19的目标是利用几十年来的研究所获得的知识， 梅毒的有效疫苗。发展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候选疫苗的遗传变异 为疫苗开发提供信息，以及ii）现代梅毒菌株的分离，这最能反映遗传 背景和毒力特性的循环病原体，可用于动物 免疫实验后进行攻毒。这些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- 感染患者提取和富集梅毒螺旋体DNA，并进行下一代全 对梅毒病原体的几百个基因组进行基因组测序。这些样本是从 地理上不同的地点，将提供更深入的了解抗原的变异性， 我们选择的候选疫苗的基因编码差异。此外，我们将隔离 来自收集自以下组织的生物样品（原发性或继发性病变渗出物）的现代密螺旋体菌株 早期梅毒患者提供替代历史梅毒分离株的动物挑战实验。 我们将在这个基因组学和隔离核心中进行的工作将是其中的关键组成部分。 为开发梅毒疫苗做出了杰出的努力。

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.