Persistence and protective efficacy of a Mycobacterium tuberculosis auxotroph vaccine

被引:140
作者
Jackson, M
Phalen, SW
Lagranderie, M
Ensergueix, D
Chavarot, P
Marchal, G
McMurray, DN
Gicquel, B
Guilhot, C
机构
[1] Inst Pasteur, Unite Genet Mycobacterienne, F-75724 Paris 15, France
[2] Inst Pasteur, Lab BCG, F-75724 Paris, France
[3] Inst Pasteur, Unite Physiopathol Infect, F-75724 Paris 15, France
[4] Texas A&M Univ, Hlth Sci Ctr, Dept Med Microbiol & Immunol, College Stn, TX USA
关键词
D O I
10.1128/IAI.67.6.2867-2873.1999
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2867 / 2873
页数:7
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