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PMID: 10338493 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Persistence and protective efficacy of a Mycobacterium tuberculosis auxotroph vaccine.

Infection and immunity ·Vol. 67 ·No. 6 ·1999-06-00 ·Pages 2867-73

Jackson M, Phalen SW, Lagranderie M, Ensergueix D, Chavarot P, Marchal G, McMurray DN, Gicquel B, Guilhot C

Abstract

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.

MeSH Terms
Animals BCG Vaccine/genetics,immunology Bacterial Proteins/genetics,immunology Disease Models, Animal Female Guinea Pigs Hypersensitivity, Delayed/immunology Macrophages/microbiology Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mutagenesis Mycobacterium bovis/genetics,growth & development,immunology,pathogenicity Mycobacterium tuberculosis/genetics,growth & development,immunology,pathogenicity Peptide Synthases Purines Tuberculosis/microbiology,prevention & control Vaccines, Synthetic/genetics,immunology
Chemicals
BCG Vaccine Bacterial Proteins Purines Vaccines, Synthetic Peptide Synthases PurC protein, Bacteria
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Jackson M
Unité de Génétique Mycobactérienne, Institut Pasteur, 75724 Paris Cedex, France. [email protected]
Phalen S W
Lagranderie M
Ensergueix D
Chavarot P
Marchal G
McMurray D N
Gicquel B
Guilhot C
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.67.6.2867-2873.1999
Email
[email protected]
Published
1999-06-00
Pages
2867-73
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC96594
Subset
IM
Grants
NIAID NIH HHS · AI 35207 · United States
External Links
PubMed source DOI: 10.1128/IAI.67.6.2867-2873.1999 PMC Full Text View journal details
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