Vaccine-mediated control of bacterial virulence regulation and infection

项目概述：金黄色葡萄球菌（SA），包括耐甲氧西林（MRSA）， 皮肤和软组织感染（SSTI）的最常见原因。SA导致复发 感染，特别是在免疫功能降低的高度易感患者群体中。到 迄今为止，还没有预防SA感染的疫苗在人体试验中获得成功。与此同时， 疫苗的研发在不断升级，这种病原体获得抗生素的能力也在不断升级， 阻力我们已经开发了一种新的疫苗来控制SA毒力因子的调节 生产在皮肤感染的模型中，这种疫苗诱导抗体，防止 这一调节系统和保护免受侵入性感染。在本提案中，我们旨在评估 这种疫苗策略的临床前潜力。我们将在多种情况下确定疫苗的有效性， SA感染的模型以及免疫功能降低的模型。我们的结果可以奠定 为开发有效的疫苗以预防SA感染和限制 发病机制这种疫苗可以显着改善患有癌症的患者的健康状况。 侵袭性SA感染。

PROJECT SUMMARY: Staphylococcus aureus (SA), including methicillin-resistant (MRSA), is the most common cause of skin and soft tissue infection (SSTI) in the US. SA causes recurrent infections, particularly in highly susceptible patient populations with reduced immune function. To date, no vaccine to prevent SA infection has succeeded in human trials. Meanwhile, the need for a vaccine continues to escalate, as does the ability of this pathogen to acquire antibiotic resistance. We have developed a novel vaccine to control regulation of SA virulence factor production. In models of skin infection, this vaccine induces antibodies that prevent activation of this regulator system and protect against invasive infection. In this proposal, we aim to evaluate the preclinical potential of this vaccine strategy. We will determine vaccine efficacy in multiple models of SA infection as well as models of reduced immune function. Our results could lay the groundwork for development of an efficacious vaccine to prevent SA infection and limit pathogenesis. This vaccine could significantly improve the health of patients who suffer from invasive SA infections.