Vaccine-mediated control of bacterial virulence regulation and infection

项目摘要：金黄色葡萄球菌(SA)，包括耐甲氧西林金黄色葡萄球菌(MRSA) 在美国，皮肤和软组织感染(SSTI)的最常见原因。SA导致复发 感染，特别是在免疫功能低下的高度易感患者群体中。至 到目前为止，还没有预防金黄色葡萄球菌感染的疫苗在人体试验中成功。与此同时，需要 疫苗不断升级，这种病原体获得抗生素的能力也在不断提高。 抵抗。我们已经开发了一种新的疫苗来控制SA毒力因子的调节 制作。在皮肤感染模型中，这种疫苗诱导抗体防止激活 这种调节系统可防止侵入性感染。在这份提案中，我们的目标是评估 这一疫苗策略的临床前潜力。我们将在多个方面确定疫苗的效力 金黄色葡萄球菌感染模型和免疫功能低下模型。我们的结果可能会奠定 开发预防金黄色葡萄球菌感染的有效疫苗的基础和限制 发病机制。这种疫苗可以显著改善患有癌症的患者的健康 侵袭性金黄色葡萄球菌感染。

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.