Bovis Bacille Calmette-Guérin Strains Research Articles

Novel vaccination strategies based on recombinant Mycobacterium bovis BCG

AbstractIn this manuscript, we will review the utilization of Mycobacterium bovis Bacille Calmette-Guérin (BCG) as a vaccine against tuberculosis (TB) and as a carrier system for heterologous antigens. BCG is one of the most widely used vaccines. Novel techniques in genome manipulation allow the construction of virulence-attenuated recombinant (r)-BCG strains that can be employed as homologous vaccines, or as heterologous antigen delivery systems, for priming pathogen-specific immunity against infectious diseases, including TB. Several approaches are available for heterologous antigen expression and compartmentalization in BCG and recent findings show the potential to modulate and direct the immune responses induced by r-BCG strains as desired. Recent achievements in complete genome analysis of various target pathogens, combined with a better understanding of protective pathogen-specific immune responses, form the basis for the rational design of a new generation of recombinant mycobacterial vaccines against a multitude of infectious diseases.

Mycobacterium bovis BCG-based vaccines against tuberculosis: novel developments

Mycobacterium bovis Bacille Calmette–Guérin (BCG) is one of the most widely used vaccines. Modern techniques in genome manipulation allow the construction of recombinant (r)-BCG strains that can be employed as highly immunogenic vaccines against tuberculosis (TB) with an enhanced safety profile. In addition, the development of novel procedures to cultivate BCG will allow the large-scale production of future BCG-based vaccines.

Analysis of stress- and host cell-induced expression of the Mycobacterium tuberculosis inorganic pyrophosphatase.

The gene encoding the inorganic pyrophosphatase (PPase) of the intracellular pathogen Legionella pneumophila is induced during intracellular infection, but is constitutively expressed in Escherichia coli. The causative agent of tuberculosis, Mycobacterium tuberculosis, contains a well conserved copy of PPase. We sought to determine if expression of the M. tuberculosis PPase is regulated by the intracellular environment. A strain of Mycobacterium bovis bacille Calmette-Guérin (BCG) was constructed in which the Aequoria victoria green fluorescent protein (GFP) is controlled by the promoter of the M. tuberculosis ppa gene. After prolonged exposure of the recombinant BCG strain within murine bone-marrow-derived macrophages, there was no observed increased activity of the ppa promoter. Furthermore, there was no change in promoter activity after exposure to various stress stimuli such as reduced pH, osmotic shock, nutrient limitation or oxidative stress. These results suggest that macrophage induction of ppa is not a general phenomenon among intracellular pathogens.

Differential T Cell Responses To Mycobacteria-Secreted Proteins Distinguish Vaccination With Bacille Calmette-Guerin From Infection With Mycobacterium Tuberculosis

The immune responses of healthy recipients of Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine, tuberculosis (TB) patients, and contacts of TB patients were examined to three major secretory proteins of Mycobacterium tuberculosis, MPB59, MPB64, and MPB70. MPB59 evoked a T cell response in 78% of BCG vaccines, 62% of TB patients, and 60% of contacts. MPB64 and MPB70 were recognized by < 15% of BCG vaccinees, half of TB patients, and three-quarters of contacts. TB and leprosy patients had antibody responses to MPB59, but few had antibodies to MPB64 or MPB70. Hybridization of mycobacterial DNA with specific gene probes demonstrated the absence of a gene for MBP64 in the vaccine strain of BCG, but the MPB70 gene was found in all virulent and vaccine BCG strains tested. Since MPB64 and MPB70 can induce delayed-type hypersensitivity reactions in infected animals, either of these proteins may have potential as skin test reagents for detecting infection with M. tuberculosis.