• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Feb 28, 1995; 92(5): 1530–1534.
PMCID: PMC42553

Protective immunity against tuberculosis induced by vaccination with major extracellular proteins of Mycobacterium tuberculosis.

Abstract

Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, is the world's leading cause of death in humans from a single infectious agent. A safe and effective vaccine against this scourge is urgently needed. This study demonstrates that immunization with the 30-kDa major secretory protein, alone or in combination with other abundant extracellular proteins of M. tuberculosis, induces strong cell-mediated immune responses and substantial protective immunity against aerosol challenge with virulent M. tuberculosis bacilli in the highly susceptible guinea pig model of pulmonary tuberculosis. Protection is manifested by decreased clinical illness including decreased weight loss, reduced mortality, and decreased growth of M. tuberculosis in the lungs and spleens of immunized animals compared with sham-immunized controls. This study demonstrates that purified major extracellular proteins of M. tuberculosis are candidate components of a subunit vaccine against tuberculosis and provides compelling support for the concept that extracellular proteins of intracellular pathogens are key immunoprotective molecules.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kochi A. The global tuberculosis situation and the new control strategy of the World Health Organization. Tubercle. 1991 Mar;72(1):1–6. [PubMed]
  • Fine PE. The BCG story: lessons from the past and implications for the future. Rev Infect Dis. 1989 Mar-Apr;11 (Suppl 2):S353–S359. [PubMed]
  • Quinn TC. Interactions of the human immunodeficiency virus and tuberculosis and the implications for BCG vaccination. Rev Infect Dis. 1989 Mar-Apr;11 (Suppl 2):S379–S384. [PubMed]
  • Schlesinger LS, Bellinger-Kawahara CG, Payne NR, Horwitz MA. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J Immunol. 1990 Apr 1;144(7):2771–2780. [PubMed]
  • Schlesinger LS. Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. J Immunol. 1993 Apr 1;150(7):2920–2930. [PubMed]
  • Clemens DL, Horwitz MA. Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J Exp Med. 1995 Jan 1;181(1):257–270. [PMC free article] [PubMed]
  • Armstrong JA, Hart PD. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med. 1971 Sep 1;134(3 Pt 1):713–740. [PMC free article] [PubMed]
  • Harth G, Clemens DL, Horwitz MA. Glutamine synthetase of Mycobacterium tuberculosis: extracellular release and characterization of its enzymatic activity. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9342–9346. [PMC free article] [PubMed]
  • Blander SJ, Horwitz MA. Vaccination with the major secretory protein of Legionella pneumophila induces cell-mediated and protective immunity in a guinea pig model of Legionnaires' disease. J Exp Med. 1989 Mar 1;169(3):691–705. [PMC free article] [PubMed]
  • Blander SJ, Horwitz MA. Vaccination with the major secretory protein of Legionella induces humoral and cell-mediated immune responses and protective immunity across different serogroups of Legionella pneumophila and different species of Legionella. J Immunol. 1991 Jul 1;147(1):285–291. [PubMed]
  • Blander SJ, Horwitz MA. Major cytoplasmic membrane protein of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, induces protective immunity in a guinea pig model of Legionnaires' disease. J Clin Invest. 1993 Feb;91(2):717–723. [PMC free article] [PubMed]
  • Pal PG, Horwitz MA. Immunization with extracellular proteins of Mycobacterium tuberculosis induces cell-mediated immune responses and substantial protective immunity in a guinea pig model of pulmonary tuberculosis. Infect Immun. 1992 Nov;60(11):4781–4792. [PMC free article] [PubMed]
  • Andersen P. Effective vaccination of mice against Mycobacterium tuberculosis infection with a soluble mixture of secreted mycobacterial proteins. Infect Immun. 1994 Jun;62(6):2536–2544. [PMC free article] [PubMed]
  • Mehlert A, Young DB. Biochemical and antigenic characterization of the Mycobacterium tuberculosis 71kD antigen, a member of the 70kD heat-shock protein family. Mol Microbiol. 1989 Feb;3(2):125–130. [PubMed]
  • Allison AC, Byars NE. An adjuvant formulation that selectively elicits the formation of antibodies of protective isotypes and of cell-mediated immunity. J Immunol Methods. 1986 Dec 24;95(2):157–168. [PubMed]
  • Borremans M, de Wit L, Volckaert G, Ooms J, de Bruyn J, Huygen K, van Vooren JP, Stelandre M, Verhofstadt R, Content J. Cloning, sequence determination, and expression of a 32-kilodalton-protein gene of Mycobacterium tuberculosis. Infect Immun. 1989 Oct;57(10):3123–3130. [PMC free article] [PubMed]
  • Zhang Y, Lathigra R, Garbe T, Catty D, Young D. Genetic analysis of superoxide dismutase, the 23 kilodalton antigen of Mycobacterium tuberculosis. Mol Microbiol. 1991 Feb;5(2):381–391. [PubMed]
  • Matsuo K, Yamaguchi R, Yamazaki A, Tasaka H, Yamada T. Cloning and expression of the Mycobacterium bovis BCG gene for extracellular alpha antigen. J Bacteriol. 1988 Sep;170(9):3847–3854. [PMC free article] [PubMed]
  • Nagai S, Wiker HG, Harboe M, Kinomoto M. Isolation and partial characterization of major protein antigens in the culture fluid of Mycobacterium tuberculosis. Infect Immun. 1991 Jan;59(1):372–382. [PMC free article] [PubMed]
  • Orme IM, Collins FM. Protection against Mycobacterium tuberculosis infection by adoptive immunotherapy. Requirement for T cell-deficient recipients. J Exp Med. 1983 Jul 1;158(1):74–83. [PMC free article] [PubMed]
  • Fok JS, Ho RS, Arora PK, Harding GE, Smith DW. Host-parasite relationships in experimental airborne tuberculosis. V. Lack of hematogenous dissemination of Mycobacterium tuberculosis to the lungs in animals vaccinated with Bacille Calmette-Guérin. J Infect Dis. 1976 Feb;133(2):137–144. [PubMed]
  • Smith DW, McMurray DN, Wiegeshaus EH, Grover AA, Harding GE. Host-parasite relationships in experimental airborne tuberculosis. IV. Early events in the course of infection in vaccinated and nonvaccinated guinea pigs. Am Rev Respir Dis. 1970 Dec;102(6):937–949. [PubMed]
  • Smith DW, Wiegeshaus E, Navalkar R, Grover AA. Host-parasite relationships in experimental airborne tuberculosis. I. Preliminary studies in BCG-vaccinated and nonvaccinated animals. J Bacteriol. 1966 Feb;91(2):718–724. [PMC free article] [PubMed]
  • Cohen MK, Bartow RA, Mintzer CL, McMurray DN. Effects of diet and genetics on Mycobacterium bovis BCG vaccine efficacy in inbred guinea pigs. Infect Immun. 1987 Feb;55(2):314–319. [PMC free article] [PubMed]
  • Collins FM. Protection to mice afforded by BCG vaccines against an aerogenic challenge by three mycobacteria of decreasing virulence. Tubercle. 1985 Dec;66(4):267–276. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...