Inhaled nisin as an emergency intervention against antibiotic sensitive or resist
吸入乳链菌肽作为对抗抗生素敏感或耐药的紧急干预措施
基本信息
- 批准号:7480537
- 负责人:
- 金额:$ 29.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-03-01 至 2009-10-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAnthrax VaccinesAnthrax diseaseAntibiotic ResistanceAntibiotic TherapyAntibioticsBacillus anthracisBacillus anthracis sporeBacterial InfectionsBacterial SporesBindingBiological WarfareBioterrorismBiothraxBreathingCaringCategoriesCellsCessation of lifeCiprofloxacinClinical ResearchDevelopmentDiseaseDisease ProgressionDoseDoxycyclineDrug FormulationsEmergency SituationEngineeringEventExposure toFood PreservativesFutureGerminationGoalsHospitalsImmunityIndividualInfectionInfectious AgentInhalatorsInterventionLearningLungMilitary PersonnelMusNisinOther TherapyPeptidesPharmaceutical PreparationsPreventionPrincipal InvestigatorProcessProductionProphylactic treatmentPublic HealthRangeReproduction sporesRespiratory SystemRiskSafetySkinStandards of Weights and MeasuresSurfaceTechnologyTestingTimeToxinTreatment ProtocolsUnited States Food and Drug AdministrationVaccinationVaccinesaerosolizedanthrax toxinbasedaydesigndisorder preventiondosageemergency service responderfallsmouse modelpreventprogramsresponsesuccess
项目摘要
DESCRIPTION (provided by applicant): The deliberate release of Bacillus anthracis spores remains an imminent threat both in terms of bioterrorism and biowarfare. Individuals who inhale these spores are at extreme risk of infection and death from anthrax. Current prophylaxis and therapy in the event of B. anthracis spore inhalation fall into two categories. Vaccination to protect against future exposure, and antibiotic therapy to treat systemic bacterial infections. The commercially available anthrax vaccine requires 6 doses over 18 months for full efficacy and while there have been some non-clinical studies of post exposure vaccination, this has not yet been proven to be helpful for prevention of disease. Antibiotic therapy, usually with ciprofloxacin, is effective only after the inhaled spores germinate and grow as vegetative cells, at which time two anthrax toxins are expressed. It is possible to engineer antibiotic resistant strains of B. anthracis that would render antibiotics ineffective. B. anthracis spores themselves are inert and do not express toxin until they germinate and grow vegetatively, thus it would be of great utility to have a product which could neutralize inhaled spores prior to germination thus keeping them inert until they can be cleared from the body. The lantibiotic peptide nisin has the unique capacity to bind to and neutralize bacterial spores, including B. anthracis spores and spores isolated from antibiotic-resistant B. anthracis. By binding to the spore surface, nisin arrests the germination process. Nisin has received a "Generally Recognized As Safe" designation from the FDA, is currently widely used as a food preservative, and is used in various topical veterinary products. The goal of this submission is to develop an inhaled nisin formulation that could be used in addition to conventional antibiotics and other anthrax therapies in the event of exposure to inhaled anthrax spores. It is the only know intervention that can be used on an emergency basis to neutralize inhaled spores. This product would be deployed with first responders and military personnel in the form of a disposable inhaler to be used immediately after suspected spore inhalation to neutralize the inhaled spores in the lungs prior to germination and toxin production. This proposal will test the capacity of nisin to protect animals against pulmonary challenge with anthrax spores and examine the safety of nisin delivery to the lungs. PUBLIC HEALTH RELEVANCE: Anthrax remains a serious bioterrorism/biowarfare threat. Spores of Bacillus anthracis are relatively easy to produce and disseminate, and the "weaponization" process makes these spores even more effective bioterrorism agents. One of the lessons learned from the events of 2001 is that infections resulting from deliberate exposure to anthrax spores, especially weaponized spores, can be very difficult to treat. In the event of an attack with anthrax spores, victims exposed to the spores can receive several treatments to try to prevent disease progression. The current standard of care is long term dosing of antibiotics like ciprofloxin or doxycycline which can be administered for as long as 60 days. Vaccines, like Biothrax (Emergent Biosolutions) can also be administered immediately after exposure with the hope of generating some protective immunity, but this vaccine requires six doses over eighteen months to be fully protective. Currently, there are no products specifically designed to neutralize spores in the respiratory tract. Anthrax spores are the infectious agent of B. anthracis, but by themselves are inert and not pathogenic. The spores must germinate and grow vegetatively to express toxins, and being able to neutralize inhaled spores in the lungs and prevent their germination could help prevent disease. Optimally, such a neutralizer, which prevent the germination of all spores, but neutralization of even a percentage of the spores would give the other therapies a better chance for success. There is an immediate need for a product specifically designed to neutralize anthrax spores in the respiratory tract. This product should be extremely safe and be able to be formulated in such a way that it can be used in the field in situations and in hospitals where anthrax spore exposure is suspected as an additional layer of protection beyond the use of antibiotics, post exposure vaccinations and other therapies in development. This submission proposes to develop an inhaled product that can neutralize inhaled anthrax spores before they germinate and grow to cause systemic and fatal disease. This product is intended as an addition to other anthrax therapies. Currently there is no such product is available.
描述(由申请方提供):故意释放炭疽芽孢杆菌孢子仍然是生物恐怖主义和生物战方面的一个迫在眉睫的威胁。吸入这些孢子的人有极高的感染和死于炭疽的风险。B事件的当前预防和治疗。吸入炭疽孢子分为两类。接种疫苗以防止未来的暴露,抗生素治疗以治疗全身性细菌感染。市售炭疽疫苗需要在18个月内接种6剂才能完全发挥功效,虽然已经进行了一些接触后疫苗接种的非临床研究,但尚未证明这有助于预防疾病。抗生素治疗,通常与环丙沙星,是有效的,只有在吸入孢子发芽和生长为营养细胞,在这个时候两个炭疽毒素表达。有可能对B的抗生素抗性菌株进行工程改造。炭疽病会使抗生素失效。B。炭疽孢子本身是惰性的,并且直到它们发芽和植物性生长才表达毒素,因此,具有一种能够在发芽之前中和吸入的孢子从而保持它们惰性直到它们能够从体内清除的产品将是非常有用的。羊毛硫抗生素肽乳链菌肽具有结合并中和细菌孢子(包括B)的独特能力。炭疽孢子和从抗炭疽菌B分离的孢子。炭疽病通过结合到孢子表面,乳链菌肽阻止萌发过程。乳链菌肽已获得FDA的“公认安全”称号,目前被广泛用作食品防腐剂,并用于各种局部兽药产品。本次提交的目的是开发一种吸入型乳酸链球菌素制剂,在暴露于吸入型炭疽孢子的情况下,该制剂可作为传统抗生素和其他炭疽治疗药物的补充。这是唯一已知的可以在紧急情况下用于中和吸入孢子的干预措施。该产品将以一次性吸入器的形式部署给第一反应者和军事人员,在疑似孢子吸入后立即使用,以在萌发和毒素产生之前中和肺部吸入的孢子。这项建议将测试乳酸链球菌素保护动物免受炭疽孢子肺部攻击的能力,并研究乳酸链球菌素输送到肺部的安全性。公共卫生相关性:炭疽仍然是一个严重的生物恐怖主义/生物战威胁。炭疽芽孢杆菌的孢子相对容易产生和传播,"武器化"过程使这些孢子成为更有效的生物恐怖主义制剂。从2001年事件中吸取的教训之一是,故意接触炭疽孢子,特别是武器化的孢子,造成的感染可能非常难以治疗,在炭疽孢子袭击事件中,接触孢子的受害者可以接受几种治疗,以防止疾病进展。目前的护理标准是长期给药抗生素,如环丙沙星或多西环素,可以给药长达60天。疫苗,如Biothrax(紧急生物解决方案)也可以在接触后立即接种,希望产生一些保护性免疫,但这种疫苗需要在18个月内接种6次才能完全保护。目前,没有专门设计用于中和呼吸道中孢子的产品。炭疽孢子是B的传染因子。炭疽,但本身是惰性的,不是致病的。孢子必须发芽并生长以表达毒素,并且能够中和肺部吸入的孢子并阻止其发芽可以帮助预防疾病。最理想的是,这种中和剂,它防止所有孢子的萌发,但即使是一个百分比的孢子的中和也会给其他疗法更好的成功机会。迫切需要一种专门设计用于中和呼吸道中炭疽孢子的产品。该产品应非常安全,并能够以这样的方式配制,即它可以在怀疑炭疽孢子暴露的情况下和医院中使用,作为除使用抗生素、暴露后疫苗接种和其他正在开发的疗法之外的额外保护层。该提交文件建议开发一种吸入产品,可以在吸入的炭疽孢子发芽和生长导致全身性和致命性疾病之前中和它们。该产品旨在作为其他炭疽治疗的补充。目前还没有这样的产品。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Kenneth Alibek其他文献
Kenneth Alibek的其他文献
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{{ truncateString('Kenneth Alibek', 18)}}的其他基金
Nisin as a decontaminant for B. anthracis spores on human skin
乳链菌肽作为人体皮肤上炭疽芽孢杆菌孢子的净化剂
- 批准号:
7201607 - 财政年份:2006
- 资助金额:
$ 29.98万 - 项目类别:
Nisin as a decontaminant for B. anthracis spores on human skin
乳链菌肽作为人体皮肤上炭疽芽孢杆菌孢子的净化剂
- 批准号:
7054889 - 财政年份:2006
- 资助金额:
$ 29.98万 - 项目类别:
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