A multivalent vaccine for Staphylococcus aureus

金黄色葡萄球菌多价疫苗

• 批准号: 10057219
• 负责人: JON OSCHERWITZ
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10057219
• 关键词: Adjuvant; Aerosols; Amino Acids; Antibodies; Antigens; Bacillus anthracis; Bacteria; Bacterial Endocarditis; Biological Assay; Centers for Disease Control and Prevention (U.S.); Chickenpox; Clinical Trials; Communicable Diseases; Communities; Community Hospitals; Cutaneous; Cytolysins; Cytotoxin; Data; Development; Disease; Epitopes; Evaluation; Failure; Gram-Positive Bacteria; Growth; HIV-1; Hemolysin; Hepatitis; Hospitals; Host Defense; Human; Humoral Immunities; Immune Sera; Immunity; Immunization; In Vitro; Individual; Infection; Infectious Skin Diseases; Injury; Lung; Malaria; Mediating; Medical Economics; Methicillin Resistance; Modeling; Molecular; Monoclonal Antibodies; Morbidity - disease rate; Mus; Oryctolagus cuniculus; Panton-Valentine leukocidin; Performance; Pertussis; Phase; Pneumonia; Poliomyelitis; Production; Public Health; Reproduction spores; Sepsis; Services; Specificity; Staphylococcal Vaccines; Staphylococcus aureus; Staphylococcus aureus infection; Structure; Superantigens; Toxin; United States; Vaccination; Vaccines; Validation; Vancomycin; Virulence; Virulence Factors; Virulent; Virus-like particle; Work; alpha Toxin; cytotoxicity; design; economic impact; efficacy evaluation; human disease; immunogenic; leukotoxin; member; methicillin resistant Staphylococcus aureus; military veteran; mortality; mouse model; nanoparticle; neutralizing antibody; pathogen; prevent; protective efficacy; prototype; resistant strain; response; success; tissue injury; vaccine trial

Staphylococcus aureus is a gram positive bacteria that possesses a multitude of virulence factors. It is a frequent and severe pathogen in hospitals and of increasing concern in the community, where it results in severe skin infections, pneumonia, sepsis and lethal bacterial endocarditis. A significant proportion of these infections are the result of methicillin-resistant S. aureus (MRSA). We have developed a highly immunogenic prototype nanoparticle vaccine capable of rapidly eliciting antibody against the pore neutralizing determinant (PND) within alpha toxin (AT), a ubiquitous and critical virulence factor of MRSA. Previous work has demonstrated that Ab against the PND is highly efficacious in preventing tissue injury and bacterial growth in a rigorous mouse dermonecrosis model, and in protecting mice in a lethal model of S. aureus pneumonia. In this project, we will utilize the human hepatitis core antigen platform to develop nanoparticle vaccines capable of neutralizing the key leukotoxins including gamma toxin, Panton Valentine leukocidin, LukED and LukGH, which are critical, secreted virulence factors which enable S. aureus to evade host immunity, and a nanoparticle vaccine targeting the previously validated PND of AT. The vaccines emerging from these studies will be uniquely effective against MRSA infections and will ideally be the basis of an efficacious, multivalent nanoparticle vaccine for MRSA.

金黄色葡萄球菌是一种革兰氏阳性细菌，具有多种毒力 因素。这是医院常常且严重的病原体，并且越来越关注 社区，导致严重的皮肤感染，肺炎，败血症和致命的社区 细菌性心内膜炎。这些感染中很大一部分是 耐甲氧西林金黄色葡萄球菌（MRSA）。我们已经开发了高度免疫原性 原型纳米颗粒疫苗，能够快速引起孔的抗体 α毒素（AT）中的中和决定因素（PND），无处不在且关键 MRSA的毒力因子。以前的工作表明，针对PND的AB是 高效防止严格的小鼠组织损伤和细菌生长 皮肤分数模型，以及在金黄色葡萄球菌肺炎的致命模型中保护小鼠。 在这个项目中，我们将利用人类肝炎核心抗原平台开发 纳米颗粒疫苗能够中和包括伽马在内的关键白细胞毒素 毒素，Panton Valentine Liukocidin，Luked和Lukgh，这是至关重要的 毒力因子使金黄色葡萄球菌能够逃避宿主的免疫力和纳米颗粒 靶向先前验证的AT的疫苗。疫苗从 这些研究将对MRSA感染具有独特的有效性，理想情况下将是 MRSA有效的多价纳米颗粒疫苗的基础。