Persistence and protective efficacy of a Mycobacterium tuberculosis auxotroph vaccine
| Autor: | Brigitte Gicquel, Micheline Lagranderie, Susan W. Phalen, Christophe Guilhot, Mary Jackson, P Chavarot, Gilles Marchal, Danielle Ensergueix, David N. McMurray |
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| Předmět: |
Male
Tuberculosis Immunology Guinea Pigs Virulence Mutagenesis (molecular biology technique) Biology Microbiology Guinea pig Mycobacterium tuberculosis Mice Bacterial Proteins medicine Animals Hypersensitivity Delayed Peptide Synthases Mycobacterium bovis Mice Inbred BALB C Vaccines Synthetic Macrophages biology.organism_classification medicine.disease Virology Mice Inbred C57BL Disease Models Animal Infectious Diseases Mycobacterium tuberculosis complex Mutagenesis Purines Microbial Immunity and Vaccines BCG Vaccine Parasitology Female BCG vaccine |
| Zdroj: | ResearcherID |
| Popis: | New vaccines against tuberculosis are urgently required because of the impressive incidence of this disease worldwide and the highly variable protective efficacy of the current vaccine. The possibility of creating new live vaccines by the rational attenuation of strains from the Mycobacterium tuberculosis complex was investigated. Two auxotrophic mutants of M. tuberculosis and M. bovis BCG were constructed by disruption of one of their purine biosynthetic genes. These mutants appeared unable to multiply in vitro within mouse bone-marrow derived macrophages. They were also attenuated in vivo in the mouse and guinea pig animal models. In guinea pigs, the two mutants induced strong delayed-type hypersensitivity response to purified protein derivative. In a preliminary experiment, the two mutants were compared to the BCG vaccine for their protective efficacy in a challenge against aerosolized virulent M. tuberculosis in the guinea pig model. Both mutants conferred some level of protection. These experiments demonstrate that the rational attenuation of M. tuberculosis could lead to the design of new candidate live vaccines against tuberculosis. |
| Databáze: | OpenAIRE |
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