EFFICACY AND SAFETY OF LIVE ATTENUATED MYCOBACTERIUM TUBERCULOSIS VACCINES

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 结核病（TB）仍然是全球健康负担，需要安全和新型疫苗策略。 由于BCG作为TB疫苗的局限性，减毒活结核分枝杆菌突变体受到关注。 使用减毒活结核分枝杆菌突变体的关键是它们在非人灵长类动物中的安全性文件。 在这项研究中，我们描述的研究，评估安全性和有效性的两个活减毒M。结核病双缺失疫苗株（mc^2 6020，莱莎 2018 - 02 - 22 00：00：00（RD1 panCD）。 mc^2 6020是一种快速清除的菌株，mc^2 6030是一种持久性菌株。 为了测试安全性，皮内注射9 × 10^6 CFU/mL（相当于人体BCG剂量的50倍）的mc^2 6020或mc^2 6030。 两种减毒活M.结核病疫苗株是安全的，耐受性良好。 在高剂量支气管内用强毒M.结核病，与mc^2 6020、mc^2 6030和未接种疫苗的对照组相比，BCG接种疫苗的动物具有减少的病理学。 非复制型和限制复制型减毒活M.结核病候选疫苗是结核病疫苗接种BCG的安全替代品。

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.