Details

Autor(en) / Beteiligte

• Larsen, Michelle H
• Biermann, Karolin
• Chen, Bing
• Hsu, Tsungda
• Sambandamurthy, Vasan K
• Lackner, Andrew A
• Aye, Pyone Pyone
• Didier, Peter
• Huang, Dan
• Shao, Linyun
• Wei, Huiyong
• Letvin, Norman L
• Frothingham, Richard
• Haynes, Barton F
• Chen, Zheng W
• Jacobs, William R

Titel

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

Ist Teil von

• Vaccine, 2009-07, Vol.27 (34), p.4709-4717

Ort / Verlag

Kidlington: Elsevier Ltd

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 mc2 6020 (Δ lysA Δ panCD ) and mc2 6030 (Δ RD1 Δ panCD ) in cynomolgus macaques. In murine models, mc2 6020 is rapidly cleared while mc2 6030 persists. Both mc2 6020 and mc2 6030 were safe and well tolerated in cynomolgus macaques. Following a high-dose intrabronchial challenge with virulent M. tuberculosis , mc2 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 mc2 6030 vaccinates, but survival did not differ among the groups.