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: 8172985
• 负责人: Michelle H Larsen
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172985
• 关键词: Attenuated; Clinical; Computer Retrieval of Information on Scientific Projects Database; Dose; Funding; Grant; Human; Institution; Life; Macaca; Modeling; Mus; Mycobacterium tuberculosis; Pathology; Research; Research Personnel; Resources; Safety; Saline; Source; Tuberculosis; Tuberculosis Vaccines; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; Virulent; global health; improved; mutant; nonhuman primate; vaccination against tuberculosis; vaccine candidate

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 vaccines are needed. BCG has limitations as a TB vaccine so we have focused on live attenuated Mycobacterium tuberculosis mutants as vaccine candidates. Prior to human studies, however, it is necessary to demonstrate safety in non-human primates (NHP). In this study, we evaluate the safety and efficacy of two live attenuated M. tuberculosis double deletion vaccine strains mc^2 6020 (delta lysA delta panCD) and mc^2 6030 (delta RD1 delta panCD) in cynomolgus macaques. In murine models, mc^2 6020 is rapidly cleared while mc^2 6030 persists. Both mc^2 6020 and mc^2 6030 were safe and well tolerated in cynomolgus macaques. Following a high-dose intrabronchial challenge with virulent M. tuberculosis, mc^2 6020-vaccinates were afforded a level of protection intermediate between that elicited by BCG vaccination and no vaccination. BCG vaccinates had reduced tuberculosis-associated pathology and improved clinical scores as compared to saline and mc^2 6030 vaccinates, but survival did not differ among the groups.

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，需要安全疫苗。 BCG作为结核病疫苗有局限性，因此我们专注于活着的结核分枝杆菌突变体作为候选疫苗。 但是，在进行人类研究之前，有必要证明非人类灵长类动物（NHP）的安全性。在这项研究中，我们评估了两种活结核分枝杆菌双缺失疫苗菌株MC^2 6020（Delta Lysa Delta Pancd）和MC^2 6030（Delta RD1 Delta Pancd）在Cynomolgus Macaques中的安全性和功效。 在鼠模型中，MC^2 6020迅速清除，而MC^2 6030持续存在。 MC^2 6020和MC^2 6030均安全且在cynomolgus猕猴中的耐受性良好。在对结核分枝杆菌的高剂量内挑战之后，MC^2 6020-Vaccinates被提供了一种在BCG疫苗接种和无疫苗接种引起的保护水平。与盐水和MC^2 6030接种疫苗相比，BCG疫苗接种降低了结核病相关的病理，并提高了临床评分，但两组之间的生存率没有差异。