A New Approach to Staphylococcus aureus Vaccine Development - Resubmission 01

金黄色葡萄球菌疫苗开发的新方法 - 重新提交 01

• 批准号: 8892992
• 负责人: Robert S. Daum
• 金额: $ 51.7万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8892992
• 关键词: Adjuvant; Animals; Antibodies; Antigens; B-Lymphocytes; Bacteremia; Basic Science; Blood Circulation; Cells; Cellular Immunity; Cessation of life; Clinical; Collaborations; Collection; Combined Vaccines; Communities; Cutaneous; Disease; Drug resistance; Elements; Epidemic; Evaluation; Failure; Goals; Health; Hospitalization; Hospitals; Host Defense; Host Defense Mechanism; Humoral Immunities; Immune; Immunity; Immunoglobulin A; Immunoglobulin G; Immunologics; Immunology; Incidence; Incidence Study; Infection; Infectious Skin Diseases; Knowledge; Laboratories; Lead; Lesion; Letters; Lymphocyte Subset; Measures; Mediating; Methicillin; Methicillin Resistance; Modeling; Monobactams; Morbidity - disease rate; Mouse Strains; Mus; Pathway interactions; Phagocytes; Pneumonia; Population; Prevention; Production; Protocols documentation; Recombinant Proteins; Regulatory T-Lymphocyte; Research; Research Personnel; Resistance; Rodent Model; Sepsis; Serum; Severities; Site; Skin; Skin Tissue; Soft Tissue Infections; Staphylococcus aureus; Syndrome; T-Lymphocyte; Testing; Tissues; United States; Universities; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; Woman; Work; base; clinical efficacy; cytokine; global health; humoral immunity deficiency; insight; lipoteichoic acid; methicillin resistant Staphylococcus aureus; mortality; neutrophil; novel; novel strategies; phase II trial; prevent; protective effect; protective efficacy; research study; response; screening; vaccine development; vaccine efficacy; vaccine trial; vaccinology

DESCRIPTION (provided by applicant): Staphylococcus aureus is the most commonest cause of skin and soft tissue infections. Additionally, severe invasive S. aureus disease results in hospitalization with high mortality. An epidemic of S aureus infections has occurred in the United States in the past decade. The great majority of these infections are community associated and are methicillin-resistant, i.e. resistant to all beta-lactam antibiotics with the exception of ceftaroline. A recent annualized US study of the incidence of invasive S aureus infections estimated 600 infections occurred per 100,000 population. Therefore, there may be 1.8 million cases of S aureus infections per year in the United States alone, more than 90% of which are SSTIs. This epidemic of S aureus infections has complicated treatment and focused efforts on prevention. Prevention of Staphylococcus aureus infections by vaccination has not been simple. A number of unsuccessful vaccine trials have evaluated the protective effect of several putative protective antigens in recent years including capsular polysachharides, lipoteichoic acid, isdB and clfA. Our proposal seeks to capitalize on new ideas about how to protect against S aureus disease. Specifically, we screen antigens in collaboration with Merck Laboratories, the Brigham and Women's Hospital at Harvard University, and several derived from immunologic evaluation of convalescent sera from experimental animals to characterize protective vaccine antigen in murine models of skin infections and invasive disease with the goal to identify an optimal protective antigen combination. Following its identification, the mechanism(s) by which the new combination vaccine works will be sought. Specifically assessed will be traditional production of opsonophagocytic antibody but also the selective recruitment of lymphocyte subsets and cytokine pathways. It is expected that our combination vaccine development protocol will offer new insight into strategies for protection against invasive disease and SSTIs.

描述（由申请人提供）：金黄色葡萄球菌是皮肤和软组织感染最常见的原因。此外，严重的侵袭性金黄色葡萄球菌病会导致住院且死亡率很高。过去十年，美国发生了金黄色葡萄球菌感染的流行。这些感染中的绝大多数与社区相关，并且对甲氧西林具有耐药性，即对除头孢洛林之外的所有 β-内酰胺抗生素具有耐药性。美国最近一项关于侵袭性金黄色葡萄球菌感染发病率的年度研究估计，每 10 万人中有 600 人感染。因此，仅在美国每年就有可能有180万例金黄色葡萄球菌感染病例，其中90%以上是SSTI。此次金黄色葡萄球菌感染疫情，治疗复杂，预防为主。通过疫苗接种来预防金黄色葡萄球菌感染并不简单。近年来，许多不成功的疫苗试验评估了几种假定的保护性抗原的保护作用，包括荚膜多糖、脂磷壁酸、isdB和clfA。我们的提案旨在利用有关如何预防金黄色葡萄球菌病的新想法。具体来说，我们与默克实验室、哈佛大学布莱根妇女医院以及一些从实验动物恢复期血清的免疫学评估中获得的抗原进行筛选，以表征皮肤感染和侵袭性疾病小鼠模型中的保护性疫苗抗原，目的是确定最佳的保护性抗原组合。鉴定后，将寻求新组合疫苗的作用机制。具体评估的将是调理吞噬抗体的传统生产，以及淋巴细胞亚群和细胞因子途径的选择性募集。预计我们的组合疫苗开发方案将为预防侵入性病毒的策略提供新的见解 疾病和 SSTI。