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Infection and Immunity, June 1999, p. 2867-2873, Vol. 67, No. 6
Unité de Génétique
Mycobactérienne,1 Laboratoire du
BCG,3 and Unité de
Physiopathologie de l'Infection,4 Institut
Pasteur, 75724 Paris Cedex, France, and Department of Medical
Microbiology and Immunology, Texas A&M University Health Science
Center, College Station, Texas2
Received 21 October 1998/Returned for modification 14 December
1998/Accepted 12 March 1999
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.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Persistence and Protective Efficacy of a
Mycobacterium tuberculosis Auxotroph Vaccine
*
Corresponding author. Mailing address: Institut
Pasteur, Unité de Génétique Mycobactérienne, 25 rue du Dr. Roux, 75724 Paris cedex 15, France. Phone: 1 45 68 88 77. Fax: 1 45 68 88 43. E-mail: mjackson{at}pasteur.fr.
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