Live Vector Vaccines Against Agents of Bioterror

针对生物恐怖分子的活载体疫苗

• 批准号: 7214646
• 负责人: James P. Nataro
• 金额: $ 177.41万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7214646
• 关键词: Aerosols; Animals; Anthrax disease; Attenuated; Award; Bacterial Vaccines; Biological; Botulism; Characteristics; Chemicals; Development; Dose; Ensure; Enteral; Equilibrium; Human; Immune response; Immunity; Immunization; Immunization Programs; Individual; Infectious Agent; Life; Mails; Maryland; Mucous Membrane; Passive Immunization; Phase; Plague; Play; Role; Route; Safety; Schools; Series; Subunit Vaccines; Testing; Therapeutic Intervention; Treatment Protocols; United States; Universities; Vaccination; Vaccines; Week; assault; biodefense; experience; gastrointestinal; novel therapeutics; response; vaccine development; vector vaccine

DESCRIPTION (provided by applicant): The United States is under a genuine threat of biological attack. Whereas it has long been known that our enemies were capable of biological assault, only since September 2001 has it become clear that this threat is real. Unfortunately, the US is woefully unprepared to respond to biological attack. While rapid identification of released agents, novel therapeutic interventions and passive immunization will have vital roles to play in biodefense, there is no substitute for pre-existing immunity to the major threats. This immunity can either be provided before such agents are released, or can be provided soon after release has been detected. Unfortunately, for most infectious agents it is not currently feasible to provide rapid administration of vaccines that provide equally rapid protection. Moreover, it will be vital to ensure that any immunization program have both a high level of safety as well as public acceptance. We therefore envision a response strategy which includes live attenuated enteric bacterial vaccines. These vaccines would be very safe, and would elicit both mucosal and systemic responses. After just a single dose, they would protect many exposed to bioattack, and within one week of immunization. The protected would likely be those exposed to small or natural levels of exposure, such as postal workers handling contaminated mail. However, it is anticipated that some victims would be exposed to supra-normal inocula, typically by the aerosol or gastrointestinal routes. For these individuals, a protective vaccination regimen could include priming with the mucosal agent, followed by on-demand boosting with parenterally administered subunit vaccine. After boosting, the recipients would be expected to generate fast, vigorous, balanced immune responses, which would protect them at the level of the mucosa and via both Th1 and Th2 systemic components. This U19 will combine the vast experience of the University of Maryland School Center for Vaccine Development and the Chemical and Biological Defence Center, Porton Down in the development of enteric vaccines against anthrax, plague and botulism. The products developed will be tested in animals and the characteristics of prime-boost responses determined. During the term of the award, we will generate a series of vaccine candidates for immediate Phase 1 human trials.

描述（由申请人提供）：美国处于生物攻击的真正威胁之下。虽然我们早就知道我们的敌人有能力进行生物攻击，但直到2001年9月才清楚地看到这种威胁是真实的。不幸的是，美国对应对生物攻击毫无准备。虽然快速识别释放的药剂，新的治疗干预措施和被动免疫将在生物防御中发挥重要作用，但对主要威胁的预先存在的免疫力是不可替代的。这种免疫性可以在这些试剂释放之前提供，或者可以在检测到释放之后不久提供。不幸的是，对于大多数传染性病原体，提供同样快速保护的疫苗的快速施用目前是不可行的。此外，确保任何免疫接种计划都具有高水平的安全性和公众接受度至关重要。因此，我们设想了一种包括减毒活肠道细菌疫苗的应答策略。这些疫苗将是非常安全的，并会引起粘膜和全身反应。仅仅一剂之后，它们就可以保护许多暴露于生物攻击的人，并且在免疫后一周内。受保护的可能是那些暴露于小或自然暴露水平的人，例如处理受污染邮件的邮政工作人员。然而，预计一些受害者会接触到超常的接种物，通常是通过气雾剂或胃肠道途径。对于这些个体，保护性疫苗接种方案可以包括用粘膜剂引发，然后用胃肠外施用的亚单位疫苗按需加强。在加强免疫后，预期接受者将产生快速、有力、平衡的免疫应答，这将在粘膜水平上并通过Th 1和Th 2系统组分保护它们。这种U19将联合收割机结合马里兰州大学疫苗开发学校中心和波顿唐化学和生物防御中心在开发炭疽、鼠疫和肉毒杆菌中毒肠内疫苗方面的丰富经验。开发的产品将在动物中进行测试，并确定引发-加强反应的特征。在该奖项的期限内，我们将产生一系列候选疫苗，立即进行1期人体试验。

项目成果

A Yersinia pestis guaBA mutant is attenuated in virulence and provides protection against plague in a mouse model of infection.

• DOI: 10.1016/j.micpath.2010.01.005
• 发表时间: 2010-05
• 期刊: Microbial pathogenesis
• 影响因子: 3.8
• 作者: Oyston PC;Mellado-Sanchez G;Pasetti MF;Nataro JP;Titball RW;Atkins HS
• 通讯作者: Atkins HS

An anthrax subunit vaccine candidate based on protective regions of Bacillus anthracis protective antigen and lethal factor.

• DOI: 10.1016/j.vaccine.2010.07.075
• 发表时间: 2010-09-24
• 期刊: VACCINE
• 影响因子: 5.5
• 作者: Baillie, Les W.;Huwar, Theresa B.;Moore, Stephen;Mellado-Sanchez, Gabriela;Rodriguez, Liliana;Neeson, Brendan N.;Flick-Smith, Helen C.;Jenner, Dominic C.;Atkins, Helen S.;Ingram, Rebecca J.;Altmann, Danny M.;Nataro, James P.;Pasetti, Marcela F.
• 通讯作者: Pasetti, Marcela F.

Characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain.

使用条件毒力菌株表征鼠疫感染的全身性和肺炎鼠模型。

• DOI: 10.1016/j.cimid.2012.10.005
• 发表时间: 2013
• 期刊: Comparative immunology, microbiology and infectious diseases
• 作者: Mellado-Sanchez,Gabriela;Ramirez,Karina;Drachenberg,CinthiaB;Diaz-McNair,Jovita;Rodriguez,AnaL;Galen,JamesE;Nataro,JamesP;Pasetti,MarcelaF
• 通讯作者: Pasetti,MarcelaF