Encapsulated Vaccines Against Select Agents

针对特定病原体的封装疫苗

• 批准号: 7846509
• 负责人: ALLISON R FICHT
• 金额: $ 7.31万
• 依托单位: NANORELEASE TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-05 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7846509
• 关键词: Acids; Adverse effects; Alginates; Animals; Attenuated; Attenuated Live Virus Vaccine; Attenuated Vaccines; Award; Biological Models; Biological Warfare; Biopolymers; Bioterrorism; Brucella; Brucella Vaccine; Brucella abortus infection; Brucella melitensis; Brucellosis; Chronic; Classification; Data; Disease; Drug Formulations; Encapsulated; Enhancement Technology; Genes; Goals; Human; Immune response; Immunity; Inactivated Vaccines; Infection; Infectious Agent; Intervention; Laboratories; Life; Lipopolysaccharides; Methods; Microencapsulations; Mutagenesis; Mutation; Nature; Oral; Organism; Peptide Hydrolases; Performance; Polymers; Preparation; Proteins; Public Health; Research; Risk; Route; Safety; Source; Staging; System; Technology; Testing; Type IV Secretion System Pathway; Vaccination; Vaccine Antigen; Vaccine Design; Vaccines; Virulence Factors; Work; abortion; base; capsule; controlled release; design; expectation; improved; innovation; mouse model; mutant; novel; novel strategies; particle; pathogen; programs; safety testing; success; vaccine delivery; vaccine development; vaccine efficacy

DESCRIPTION (provided by applicant): The ultimate goal of the research proposed is the development of vaccines against intracellular pathogens. The model system to be employed is the Brucella spp, a causative agent of infectious abortion in animals (Bang's disease) and undulant fever, a chronic debilitating disease in humans. Historically, elimination of brucellosis as a public health threat has relied on the elimination of animal infection. However, the potential threat of bioterrorism or biowarfare use of this class B select agent underscores the need to develop direct intervention strategies to preserve public health. The long range goal is to develop an enabling technology for the enhancement and delivery of promising vaccines through controlled release. The objectives of this application are to entrap live, highly attenuated vaccine strains, in specialized coatings designed for controlled release, and test their efficacy in a mouse model. We propose that the use of controlled release vehicles can potentiate the use of safe but moderately protective strains and produce efficacious, marketable vaccines. We have several lines of strong preliminary data to support this work. These include i) Brucella attenuated strains developed through specific mutagenesis and characterized with regard to safety and efficacy in a mouse model and, ii) vaccination data documenting the performance of novel proteins as a robust erodible biopolymer in vaccine delivery systems. We will test our hypothesis with the following specific aims: 1) Entrap target strains in capsule formulations enabling sustained release and 2) Test the safety and efficacy of these novel encapsulated strains in a mouse model.

描述（由申请人提供）：拟议研究的最终目标是开发针对细胞内病原体的疫苗。将要采用的模型系统是布鲁氏菌，它是动物传染性流产（邦氏病）和波状热（人类慢性衰弱疾病）的病原体。从历史上看，消除作为公共卫生威胁的布鲁氏菌病依赖于消除动物感染。然而，生物恐怖主义或生物战使用这种B类选择剂的潜在威胁强调了制定直接干预战略以保护公众健康的必要性。长期目标是开发一种使能技术，通过控制释放增强和交付有希望的疫苗。本应用的目的是将高度减毒的活疫苗株包埋在专为控制释放而设计的特殊涂层中，并在小鼠模型中测试其有效性。我们建议，使用控释载体可以加强使用安全但具有适度保护作用的菌株，并生产有效的、可销售的疫苗。我们有几行强有力的初步数据来支持这项工作。这些包括i)通过特异性诱变开发的布鲁氏菌减毒菌株，并在小鼠模型中具有安全性和有效性特征；ii)记录新型蛋白质作为疫苗递送系统中强大可降解生物聚合物性能的疫苗接种数据。我们将以以下具体目标来验证我们的假设：1)在胶囊配方中捕获目标菌株，使其能够持续释放；2)在小鼠模型中测试这些新型胶囊菌株的安全性和有效性。