Multivalent Vaccines Effective Against MDR Salmonella

项目摘要-RP 2 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 自限性胃肠炎据估计，全球每年有9400万病例和155，000人死亡 年而由其他重要肠道病原体引起的疾病的发病率已经降低 由于FoodNet发起的干预措施，美国沙门氏菌病的发病率仍然很高， 2014年，每10万人中有7452例感染。NTS在预防上影响了 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。 这项建议旨在建立在我们以前的工作，我们已经开发了减毒活S。鼠伤寒沙门氏菌（S. Enteritrification，S.纽波特和S. Virchow疫苗这个项目的主要目标是证明我们的活疫苗 可提供广泛的保护，预防新界南地区的肠胃炎， 人口。为了实现这些目标，我们提出以下目标：目标1。确定候选人是否居住 减毒非伤寒沙门氏菌（S.鼠伤寒[血清群B]、沙门氏菌（S.肠炎[血清群D]、沙门氏菌（S. Virchow [C1血清群]和S.纽波特[血清群C2]）疫苗可预防胃肠炎;目的2.以识别 我们的候选减毒活链球菌的保护机制或非机制相关性。鼠伤寒 疫苗;目标3.预测NTS减毒活疫苗在目标人群中的性能;目的4.评价 活减毒沙门氏菌疫苗的多价制剂，并确定是否引发抗体， 有效对抗临床菌株，包括耐药性沙门氏菌。在这个项目结束时，我们 我预计我们将证明我们的候选NTS疫苗可以介导对 胃肠炎，我们将确定机制和非机制的保护相关性。我们也 我预计，我们将确定我们的活口服疫苗是否产生抗体， 循环的耐药菌株。最后，我们将证明我们的疫苗在靶点上具有免疫原性。 人口。如果我们成功，这些结果将为启动未来的1期临床试验铺平道路。

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.