VLP-based Vaccines for Targeting Staphylococcus Aureus β-barrel Toxins

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。我们开发了一种基于病毒样颗粒(VLP)的疫苗策略来控制SA 分泌的β-Barrel成孔毒素。在皮肤感染模型中，基于此的疫苗 方法诱导抗体，防止感染发病机制，免除宿主免疫细胞和 限制疾病。在这项提案中，我们的目标是评估这种疫苗策略的临床前潜力。 对抗各种SAβ-Barrel致孔毒素。我们将确定疫苗的免疫原性 在体内，并对金黄色葡萄球菌的定植效果。我们的结果可以为下一步的开发奠定基础 预防金黄色葡萄球菌感染，限制发病机制的有效疫苗。这种疫苗可以 显著改善金黄色葡萄球菌感染患者的健康状况。

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 virus-like particle (VLP)-based vaccine strategy to control SA secreted β-barrel pore-forming toxins. In models of skin infection, a vaccine based on this approach induces antibodies that prevent infection pathogenesis, spares host immune cells and limits disease. In this proposal, we aim to evaluate the preclinical potential of this vaccine strategy against a variety of SA β-barrel pore-forming toxins. We will determine vaccine immunogenicity in vivo, and efficacy in SA colonization. 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 SA infections.