Vaccine-mediated control of bacterial virulence regulation and infection

疫苗介导的细菌毒力调节和感染控制

基本信息

批准号：
10322119
负责人：
Seth Michael Daly
金额：
$ 37.88万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10322119
关键词：
Active Immunization Address Affinity Alleles Alpha Particles Antibiotic Resistance Antibodies Antibody Response Antimicrobial Resistance Apolipoproteins B Binding Blood Cell physiology Centers for Disease Control and Prevention (U.S.)Chronic Granulomatous Disease Clinical Community Hospitals Critical Illness Development DsRed Economic Burden Epitopes Failure Fluorescence Genetic Growth Health Human Image Immune Immunity Immunocompetent Immunosuppression Individual Infection Infectious Skin Diseases Intramuscular Job&apos s Syndrome Kinetics Life Lipase Luciferases Measures Mediating Methicillin Resistance Modeling Mus Operon Outcome Passive Immunization Pathogenesis Patients Peptide Hydrolases Peptide Vaccines Peptides Pneumonia Pre-Clinical Model Production Recurrence Regulation Regulator Genes Reporter Role Signal Transduction Skin Tissue Soft Tissue Infections Source Staphylococcus aureus Staphylococcus aureus infection Stream System Testing Therapeutic Toxin Vaccination Vaccines Virulence Virulence Factors Virus-like particle Western Blotting base cost design efficacy testing immune function immunogenicity improved improved outcome in vitro Assay in vivo in vivo imaging insight luminescence methicillin resistant Staphylococcus aureus mouse model neutralizing antibody novel strategies novel vaccines pathogen patient population peptide vaccination pre-clinical prevent prophylactic protein-histidine kinase receptor recurrent infection vaccination strategy vaccine candidate vaccine delivery vaccine development vaccine efficacy vaccine platform vaccine strategy vaccine-induced antibodies virtual

项目摘要

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.

项目摘要：金黄色葡萄球菌（SA），包括耐甲氧西林的（MRSA）为在美国，皮肤和软组织感染（SSTI）的最常见原因。 SA会反复出现感染，特别是在高度易感的患者种群中，免疫功能降低。到日期，没有预防SA感染的疫苗在人类试验中取得了成功。同时，需要疫苗继续升级，这种病原体获得抗生素的能力也是如此反抗。我们开发了一种新型疫苗来控制SA毒力因子的调节生产。在皮肤感染模型中，这种疫苗诱导了阻止激活的抗体该调节器系统并防止侵入性感染。在此提案中，我们旨在评估该疫苗策略的临床前潜力。我们将确定多个疫苗功效 SA感染的模型以及免疫功能降低的模型。我们的结果可能是开发有效疫苗以防止SA感染并限制的基础。发病。这种疫苗可以显着改善患有患者的健康侵入性SA感染。