Efficacy and Safety of Live Attenuated Persistent and Rapidly Cleared Mycobacterium Tuberculosis Vaccine Candidates in Non-Human Primates

Vaccine. 2009 Jul 23;27(34):4709-17. doi: 10.1016/j.vaccine.2009.05.050. Epub 2009 Jun 2.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BCG Vaccine / immunology
  • Bacterial Proteins / genetics
  • Body Weight
  • C-Reactive Protein / analysis
  • Carboxy-Lyases / genetics
  • Gene Deletion
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / immunology
  • Lung / pathology
  • Macaca fascicularis
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / pathogenicity*
  • Severity of Illness Index
  • Survival Analysis
  • Tuberculosis / prevention & control*
  • Tuberculosis Vaccines / adverse effects*
  • Tuberculosis Vaccines / immunology*
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology
  • Virulence Factors / genetics

Substances

  • BCG Vaccine
  • Bacterial Proteins
  • Tuberculosis Vaccines
  • Vaccines, Attenuated
  • Virulence Factors
  • Interferon-gamma
  • C-Reactive Protein
  • Carboxy-Lyases
  • LysA protein, Mycobacterium tuberculosis