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

Michelle H. Larsen, 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

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68 Scopus citations

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 mc26020 (ΔlysA ΔpanCD) and mc26030 (ΔRD1 ΔpanCD) in cynomolgus macaques. In murine models, mc26020 is rapidly cleared while mc26030 persists. Both mc26020 and mc26030 were safe and well tolerated in cynomolgus macaques. Following a high-dose intrabronchial challenge with virulent M. tuberculosis, mc26020-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 mc26030 vaccinates, but survival did not differ among the groups.

Original languageEnglish (US)
Pages (from-to)4709-4717
Number of pages9
JournalVaccine
Volume27
Issue number34
DOIs
Publication statusPublished - Jul 23 2009

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Keywords

  • BCG
  • Mycobacteria
  • Mycobacterium
  • Non-human primate
  • Safety
  • Tuberculosis
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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