Multivalent Vaccines Effective Against MDR Salmonella

有效对抗耐多药沙门氏菌的多价疫苗

基本信息

批准号：
9893804
负责人：
Sharon Mei Tennant
金额：
$ 30.48万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9893804
关键词：
Affect Agglutination Animals Antibiotic Resistance Antibodies Antigens Attenuated Attenuated Live Virus Vaccine 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 Vaccines Work aged bactericide cell motility cell type enteric pathogen experimental study immunogenic immunogenicity improved non-typhoidal Salmonella oral vaccine passive antibodies pathogenic bacteria pre-clinical prevent resistant strain vaccine efficacy

项目摘要

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)，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估计在全世界造成 9,400 万例病例和 155,000 人死亡。今年，由其他重要肠道病原体引起的疾病发病率有所下降。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、S. Newport 疫苗和 S. Virchow 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. 确定候选人是否存活。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. 确定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。预计我们将证明我们的候选 NTS 疫苗可以介导针对胃肠炎，我们还将确定保护的机械性和非机械性相关性。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最后，我们将证明我们的疫苗对目标具有免疫原性。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。