Efficacy and safety of live attenuated persistent and rapidly cleared Mycobacterium tuberculosis vaccine candidates in non-human primates.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Larsen, MH; Biermann, K; Chen, B; Hsu, T; Sambandamurthy, VK; Lackner, AA; Aye, PP; Didier, P; Huang, D; Shao, L; Wei, H; Letvin, NL; Frothingham, R; Haynes, BF; Chen, ZW; Jacobs, WR

Published Date

  • July 23, 2009

Published In

Volume / Issue

  • 27 / 34

Start / End Page

  • 4709 - 4717

PubMed ID

  • 19500524

Pubmed Central ID

  • 19500524

Electronic International Standard Serial Number (EISSN)

  • 1873-2518

Digital Object Identifier (DOI)

  • 10.1016/j.vaccine.2009.05.050

Language

  • eng

Conference Location

  • Netherlands