PDF(Pubmed)
Abstract：
In response to the global threat posed by bacterial pathogens, which are the second leading cause of death worldwide, vaccine development is challenged by the diversity of bacterial serotypes and the lack of immunoprotection across serotypes. To address this, we introduce BacScan, a novel genome-wide technology for the rapid discovery of conserved highly immunogenic proteins (HIPs) across serotypes. Using bacterial-specific serum, BacScan combines phage display, immunoprecipitation, and next-generation sequencing to comprehensively identify all the HIPs in a single assay, thereby paving the way for the development of universally protective vaccines. Our validation of this technique with Streptococcus suis, a major pathogenic threat, led to the identification of 19 HIPs, eight of which conferred 20-100% protection against S. suis challenge in animal models. Remarkably, HIP 8455 induced complete immunity, making it an exemplary vaccine target. BacScan\'s adaptability to any bacterial pathogen positions it as a revolutionary tool that can expedite the development of vaccines with broad efficacy, thus playing a critical role in curbing bacterial transmission and slowing the march of antimicrobial resistance.
摘要：
为了应对细菌病原体带来的全球威胁，是全球第二大死因，疫苗开发受到细菌血清型多样性和跨血清型缺乏免疫保护的挑战。为了解决这个问题，我们介绍BacScan,一种新的全基因组技术，用于快速发现跨血清型的保守的高免疫原性蛋白（HIP）。使用细菌特异性血清，BacScan结合了噬菌体展示，免疫沉淀,和下一代测序，以在单个测定中全面识别所有HIP，从而为开发通用保护性疫苗铺平了道路。我们用猪链球菌验证了这项技术，一个主要的致病威胁，导致了19个HIP的鉴定，其中八种在动物模型中赋予了20-100%的抗猪链球菌攻击保护。值得注意的是,HIP8455诱导完全免疫，使其成为典型的疫苗靶标。BacScan对任何细菌病原体的适应性使其成为一种革命性的工具，可以加快开发具有广泛功效的疫苗，因此在遏制细菌传播和减缓抗菌素耐药性发展方面发挥了关键作用。
