Inducing Immune Control of Bacterial Virulence Regulation

诱导细菌毒力调节的免疫控制

• 批准号: 9299851
• 负责人: Pamela Ranel Hall
• 金额: $ 22.45万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9299851
• 关键词: Abscess; Accident and Emergency department; Address; Adjuvant; Affinity; Alleles; Alpha Particles; Amino Acid Sequence; Animal Model; Antibiotic Resistance; Antibiotics; Antibodies; Antigens; Area; Bacterial Infections; Binding; Body Weight decreased; Buffers; Cell membrane; Centers for Disease Control and Prevention (U.S.); Chronic Granulomatous Disease; Clinical; Community-Acquired Infections; Control Groups; Data; Development; Diabetes Mellitus; Disease; Effectiveness; Epitopes; FDA approved; Failure; Female; Genetic Transcription; Goals; Hospitals; Human; Human Papilloma Virus Vaccine; Immune; Immune Sera; Immune response; Immunity; Immunize; Immunologics; Implant; Individual; Infection; Inflammatory Response; Job' s Syndrome; Length; Measurement; Methicillin Resistance; Modeling; Monoclonal Antibodies; Mus; Operon; Outcome; Peptide Vaccines; Peptides; Population; Prevalence; Prevention; Production; Public Health; Quantitative Reverse Transcriptase PCR; Recurrence; Regulation; Regulator Genes; Signal Transduction; Site; Skin Tissue; Soft Tissue Infections; Source; Specificity; Staphylococcus aureus; Symbiosis; Testing; Translating; United States National Institutes of Health; Vaccination; Vaccine Design; Vaccines; Virulence; Virulence Factors; Virus-like particle; Western Blotting; Work; antimicrobial; base; combat; design; human disease; immunogenicity; improved outcome; in vivo imaging; innovation; male; methicillin resistant Staphylococcus aureus; mouse model; novel strategies; novel vaccines; pathogen; peptide vaccination; prevent; protein expression; protein-histidine kinase; receptor; subcutaneous; vaccine development; vaccine effectiveness; vaccine efficacy; virtual

PROJECT SUMMARY: Staphylococcus aureus (SA), including methicillin-resistant (MRSA), is the most common cause of skin and soft tissue infection (SSTI) in the US. 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. Our goal is to demonstrate the effectiveness of virus-like particles (VLPs) as an innovative platform to induce immune control of bacterial virulence regulation. VLPs are a novel approach to the design of vaccines targeting bacterial infection and the ability of VLP-based vaccines targeting SA virulence regulation has not been investigated. Therefore, the goal of this proposal is to test the hypothesis that presentation of SA virulence regulating peptides on VLPs can be used to induce protective immunity. Importantly, unlike other platforms and experimental adjuvants, VLPs are currently used in FDA- approved vaccines (like the current HPV vaccines). Therefore, if experimental approaches using VLPs are successful in animal models, they can potentially translate into human trials fairly readily.

金黄色葡萄球菌（SA），包括耐甲氧西林（MRSA），是最常见的 皮肤和软组织感染（SSTI）的常见原因。迄今为止，还没有疫苗可以预防SA感染 在人体试验中取得了成功。与此同时，对疫苗的需求继续升级， 这种病原体获得抗生素耐药性。我们的目标是证明类病毒 颗粒（VLP）作为一个创新的平台，以诱导细菌毒力调节的免疫控制。vlp是 设计靶向细菌感染的疫苗的新方法和基于VLP的疫苗的能力 靶向SA毒力调节尚未研究。因此，本提案的目标是测试 假设VLP上SA毒力调节肽的呈递可用于诱导保护性 免疫力重要的是，与其他平台和实验佐剂不同，VLP目前用于FDA- 已批准的疫苗（如目前的HPV疫苗）。因此，如果使用VLP的实验方法 它们在动物模型中取得了成功，因此很容易转化为人体试验。