Multivalent Vaccines Effective Against MDR Salmonella

有效对抗耐多药沙门氏菌的多价疫苗

• 批准号: 10364711
• 负责人: Sharon Mei Tennant
• 金额: $ 32万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10364711
• 关键词: Affect; Agglutination; Animals; Antibiotic Resistance; Antibodies; Antigens; Attenuated; Attenuated Vaccines; Binding; CD4 Positive T Lymphocytes; CD8B1 gene; Cessation of life; Clinical; Clinical Trials; Conjugate Vaccines; Data; Disease; Elderly; Flow Cytometry; Formulation; Funding; Future; Gastroenteritis; Goals; Immunize; Incidence; Infant; Infection; Intervention; Investigational New Drug Application; Macaca mulatta; Mediating; Modeling; Multi-Drug Resistance; Mus; Oryctolagus cuniculus; Performance; Phase I Clinical Trials; Play; Reporting; Research Project Grants; Role; SIV; Salmonella; Salmonella Vaccines; Salmonella enteritidis; Salmonella typhimurium; Serum; Target Populations; Translational Research; United States Food and Drug Administration; Vaccination; Vaccine Production; Vaccines; Work; aged; bactericide; cell motility; cell type; cross immunity; enteric pathogen; experimental study; immunogenic; immunogenicity; improved; non-typhoidal Salmonella; oral vaccine; passive antibodies; pathogenic bacteria; pre-clinical; prevent; resistant strain; vaccine development; vaccine efficacy

Project summary – RP2 Non-typhoidal Salmonella (NTS) such as Salmonella Typhimurium and Salmonella Enteritidis generally cause self-limiting gastroenteritis. NTS is estimated to cause 94 million cases and 155,000 deaths worldwide each year. Whereas the incidence of disease caused by other important enteric pathogens have been reduced consequent to interventions initiated by FoodNet, the incidence of Salmonella disease in the U.S. has remained the same and was reported to be 7452 infections per 100,000 in 2014. NTS disproportionally affects the very young and the elderly. Our overall goal is to develop vaccines to provide broad protection against NTS disease. This proposal seeks to build on our previous work where we have developed live attenuated S. Typhimurium, S. Enteritidis, S. Newport and S. Virchow vaccines. The main goals of this project are to show that our live vaccines can provide broad protection against NTS gastroenteritis and that they will be effective in potential target populations. To achieve these goals, we propose the following aims: Aim 1. Determine whether candidate live attenuated non-typhoidal Salmonella (S. Typhimurium [serogroup B], S. Enteritidis [serogroup D], S. Virchow [serogroup C1] and S. Newport [serogroup C2]) vaccines can protect against gastroenteritis; Aim 2. To identify a mechanistic or non-mechanistic correlate of protection for our candidate live attenuated S. Typhimurium vaccine; Aim 3. To predict performance of live attenuated NTS vaccines in target populations; Aim 4. To evaluate a multivalent formulation of live attenuated Salmonella vaccines and determine whether elicited antibodies are effective against clinical strains including antibiotic-resistant Salmonella. At the conclusion of this project, we anticipate that we will have shown that our candidate NTS vaccines can mediate protection against gastroenteritis and we will have identified mechanistic and non-mechanistic correlates of protection. We also anticipate that we will have determined whether our live oral vaccines produce antibodies that recognize currently circulating antibiotic-resistant strains. Finally, we will have shown that our vaccines are immunogenic in target populations. If we are successful, these results will pave the way for initiating future Phase 1 clinical trials.

项目总结 – RP2 非伤寒沙门氏菌 (NTS)，例如鼠伤寒沙门氏菌和肠炎沙门氏菌，通常会引起 自限性胃肠炎。 NTS 预计将在全球范围内造成 9,400 万例病例和 155,000 人死亡 年。而由其他重要肠道病原体引起的疾病发病率已降低 由于 FoodNet 发起的干预措施，美国沙门氏菌病的发病率仍然保持在 据报道，2014 年每 10 万人中有 7452 例感染。NTS 对 年轻人和老年人。我们的总体目标是开发疫苗，为 NTS 疾病提供广泛的保护。 该提案旨在以我们之前的工作为基础，我们开发了活的减毒鼠伤寒沙门氏菌、鼠伤寒沙门氏菌。 肠炎疫苗、纽波特沙门氏菌疫苗和魏尔啸沙门氏菌疫苗。该项目的主要目标是证明我们的活疫苗 可以针对 NTS 胃肠炎提供广泛的保护，并且它们将有效针对潜在目标 人口。为了实现这些目标，我们提出以下目标： 目标 1. 确定候选人是否活着 减毒非伤寒沙门氏菌（S. Typhimurium [血清组 B]、S. Enteritidis [血清组 D]、S. Virchow [血清群 C1] 和 S. Newport [血清群 C2]) 疫苗可以预防胃肠炎；目标 2. 识别 对我们的候选减毒活鼠伤寒沙门氏菌的保护的机械或非机械相关性 疫苗;目标 3. 预测 NTS 减毒活疫苗在目标人群中的效果；目标 4. 评估 沙门氏菌减毒活疫苗的多价制剂，并确定引发的抗体是否是 有效对抗包括抗生素耐药沙门氏菌在内的临床菌株。在这个项目结束时，我们 预计我们将证明我们的候选 NTS 疫苗可以介导针对 胃肠炎，我们将确定保护的机械性和非机械性相关性。我们也 预计我们将确定我们的活口服疫苗是否产生能够识别目前的抗体 循环的抗生素耐药菌株。最后，我们将证明我们的疫苗在靶标中具有免疫原性 人口。如果我们成功，这些结果将为启动未来的一期临床试验铺平道路。