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Genetically Defined Attenuated Living Vaccine for Francisella

基因定义的弗朗西斯氏菌减毒活疫苗

基本信息

批准号：
7326979
负责人：
FRED L HEFFRON
金额：
$ 28.95万
依托单位：
VIROGENOMICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-15 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7326979
关键词：
Aerosols Affect Animals Antibiotic Resistance Arthropod Vectors Attenuated Attenuated Live Virus Vaccine Attenuated Vaccines Bacteria Biological Bioterrorism Bite Breathing Categories Centers for Disease Control and Prevention (U.S.)Complement DNA DNA Sequence Deletion Mutation Development Disease Dose Europe Food Francisella Francisella tularensis Frequencies Genes Genetic Recombination Goals Growth Guidelines Homologous Gene Human Immune Infection Ingestion International Japan Laboratories Legionella pneumophila Lesion Life Macaca mulatta Military Personnel Modeling Monkeys Mus Mutagenesis Mutation Mycobacterium tuberculosis National Security Oregon Organism Parents Play Polymerase Chain Reaction Primates Range Relative (related person)Research Research Priority Risk Role Route Russia Salmonella Salmonella typhimurium Serum Skin Specific qualifier value Surface Properties System Testing Time Tularemia United States Food and Drug Administration Vaccinated Vaccines Variant Veterinarians Virulence Virulent Water Work aerosolized attenuation base cell type gene discovery killings macrophage member mouse model mutant nonhuman primate particle pathogen programs research study success transmission process vaccine development vaccine evaluation vector

项目摘要

DESCRIPTION (provided by applicant): Tularemia is the severe and sometimes fatal disease caused by infection with Francisella tularensis. These bacteria are some of the most virulent pathogens known, requiring inoculation or inhalation with as few as 10 organisms to cause disease. Infections can be acquired in a variety of ways: bites from an arthropod vector, skin lesions, ingestion of contaminated food or water, or inhalation of aerosolized particles. Its low infectious dose and relative ease of airborne transmission led to the development of F. tularensis as a biological weapon by several national weapons programs. Because it presents a serious threat to national security, the Centers for Disease Control (CDC) classify F. tularensis as a category A select agent. Despite these criteria, there is no approved tularemia vaccine. The goal of the research described herein is to construct a rationally attenuated living vaccine against tularemia. We will build upon our previous discovery of genes required for virulence in F. tularemia, mutant derivatives of which provide protection against wild-type challenge in mice. These genes will be deleted, individually and in combinations, in the most virulent subspecies of the organism, resulting in attenuated, non-reverting, defined strains that do not specify antibiotic resistance. After confirming that these strains protect mice against wild-type challenge, we propose to test the vaccines in a non-human primate model, a necessary step to achieving FDA approval. Tularemia is the severe and sometimes fatal disease caused by infection with Francisella tularensis. Its low infectious dose and relative ease of airborne transmission led to the development of F. tularensis as a biological weapon by several national weapons programs. As there is no approved tularemia vaccine, we seek to develop a live attenuated tularemia vaccine.

描述(申请人提供)：图拉热症是一种严重的疾病，有时甚至是致命的，由感染图拉氏方济各菌引起。这些细菌是已知的最致命的病原体之一，需要接种或吸入少至10种微生物才能致病。感染可通过多种方式获得：节肢动物媒介叮咬、皮肤损伤、摄入受污染的食物或水，或吸入雾化颗粒。它的低感染剂量和相对容易的空中传播导致了图拉氏杆菌作为生物武器的发展，通过几个国家武器计划。由于它对国家安全构成严重威胁，美国疾病控制中心(CDC)将图拉氏丝虫列为A类选择因子。尽管有这些标准，但还没有批准的图拉热病疫苗。本研究的目的是构建一种合理减毒的图拉热症活疫苗。我们将建立在我们之前发现的图拉热菌毒力所需基因的基础上，这些突变的衍生品在小鼠身上提供了抵御野生型挑战的保护。这些基因将在最具毒性的有机体亚种中被单独或组合删除，导致减毒的、不可逆转的、明确的不指定抗生素耐药性的菌株。在确认这些菌株保护小鼠免受野生型挑战后，我们建议在非人类灵长类动物模型中测试疫苗，这是获得FDA批准的必要步骤。图拉热症是一种严重的，有时甚至是致命的疾病，由感染图拉氏方济各菌引起。它的低感染剂量和相对容易的空中传播导致了图拉氏杆菌作为生物武器的发展，通过几个国家武器计划。由于没有获得批准的图拉热病疫苗，我们寻求开发一种活的减毒图拉热病疫苗。