EFFICACY AND SAFETY OF LIVE ATTENUATED MYCOBACTERIUM TUBERCULOSIS VACCINES

结核分枝杆菌减毒活疫苗的功效和安全性

• 批准号: 7716315
• 负责人: Michelle H Larsen
• 金额: $ 2.36万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716315
• 关键词: Animals; Attenuated; Calmette-Guerin Bacillus; Computer Retrieval of Information on Scientific Projects Database; Documentation; Dose; Funding; Grant; Health; Human; Institution; Life; Modeling; Mycobacterium tuberculosis; Pathology; Research; Research Personnel; Resources; Safety; Source; Testing; Time; Tuberculosis; Tuberculosis Vaccines; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; Virulent; interest; intradermal injection; mutant; nonhuman primate; novel vaccines

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tuberculosis (TB) remains a global health burden for which safe and novel vaccine strategies are needed. Live attenuated Mycobacterium tuberculosis mutants are of interest because of the limitations of BCG as a TB vaccine. Critical to the use of live attenuated Mycobacterium tuberculosis mutants is their documentation of safety in non-human primates. In this study, we describe studies that evaluate the safety and efficacy of two live attenuated M. tuberculosis double deletion vaccine strains (mc^2 6020 (lysA panCD) and mc^2 6030 (RD1 panCD) in the non-human primate model. mc^2 6020 is a rapidly cleared strain and mc^2 6030 is a persistent strain. To test safety, an intradermal injection of 9 x 10^6 CFU/mL (50-times the equivalent human dose of BCG) of mc^2 6020 or mc^2 6030 was administered. Both live attenuated M. tuberculosis vaccine strains were safe and well tolerated. Following a high dose intrabronchial challenge with virulent M. tuberculosis, BCG vaccinated animals had reduced pathology compared to mc^2 6020, mc^2 6030, and unvaccinated controls. Both non-replicating and limited replicating live attenuated M. tuberculosis vaccine candidates represent safe alternatives to BCG for TB vaccination.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 结核病（TB）仍然是全球健康负担，需要安全和新颖的疫苗策略。 活结核分枝杆菌突变体引起了活力，因为BCG作为结核病疫苗的局限性。 对使用活结核分枝杆菌突变体的使用至关重要的是他们在非人类灵长类动物中安全的文献。 在这项研究中，我们描述了评估两种活结核分枝杆菌双缺失疫苗菌株（MC^2 6020（Lysa pancd）和MC^2 6030（RD1 PANCD）的研究的研究，在非人类灵长类动物模型中。MC^2 6020是一种快速清除的应变。 CFU/ML（50次MC^6020或MC^2 6030的人剂量）被施用。对照。非复制和有限的复制活结核分枝杆菌疫苗候选者代表了BCG的安全替代品。