| Literature DB >> 19500524 |
Michelle H Larsen1, Karolin Biermann, Bing Chen, Tsungda Hsu, Vasan K Sambandamurthy, Andrew A Lackner, Pyone Pyone Aye, Peter Didier, Dan Huang, Linyun Shao, Huiyong Wei, Norman L Letvin, Richard Frothingham, Barton F Haynes, Zheng W Chen, William R Jacobs.
Abstract
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 (DeltalysA DeltapanCD) and mc(2)6030 (DeltaRD1 DeltapanCD) 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.Entities:
Mesh：
Substances：
Year: 2009 PMID： 19500524 PMCID： PMC3512200 DOI： 10.1016/j.vaccine.2009.05.050
Source DB: PubMed Journal: Vaccine ISSN： 0264-410X Impact factor: 3.641