The Protective Effects of BCG Vaccination against Tuberculosis

  • Donald W. Smith
  • Ernst H. Wiegeshaus
  • Mark L. Edwards
Part of the Infectious Agents and Pathogenesis book series (IAPA)


An international conference, sponsored by the Fogarty International Center (FIC) of the National Institutes of Health in Washington, D.C., held in November 1987, entitled Research Toward the Global Control and Prevention of Tuberculosis, with an Emphasis on the Development of New Vaccines, would be expected to lead to an international research effort toward the eradication of tuberculosis. The research objectives of the FIC conference are similar to those of a conference organized in 1982 as the WHO Immunology of Tuberculosis program1 and therefore with the principal emphasis on the application of the technologies of genetic engineering and monoclonal antibody to the development of new antituberculosis vaccines. The objectives of these two research conferences suggest that tuberculosis control specialists are not satisfied with the protective effect of available BCG vaccines and the degree of their dissatisfaction is sufficiently great that scientists are being encouraged to develop new vaccines.


Environmental Mycobacterium Respiratory Route Exogenous Reinfection Rational Animal Model Hematogenous Seeding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Memorandum from a WHO meeting, 1982, Immunological research in tuberculosis, Bull. WHO 60:723–727.Google Scholar
  2. 2.
    Stead, W. W., 1967, Pathogenesis of a first episode of chronic pulmonary tuberculosis in man: Recrudescence of residuals of the primary infection or exogenous reinfection?, Am. Rev. Respir. Dis. 95:729–745.PubMedGoogle Scholar
  3. 3.
    West, J. B., 1962, Regional differences in gas exchange in the lungs of erect man, J. Appl. Physiol. 17:893–898.PubMedGoogle Scholar
  4. 4.
    Opie. E. L. ,and Aronson, J. D., 1927, Tubercle bacilli in latent tuberculous lesions and in lung tissue without tuberculous lesions, Arch. Pathol. Lab. Med. 4: 1–21.Google Scholar
  5. 5.
    Canetti, G. ,1972, Endogenous reactivation and exogenous reinfection: Their relative importance with regard to the development of non-primary tuberculosis, Bull. Int. Natl. Union Tuberc. 47:116–122.Google Scholar
  6. 6.
    Prabhakar, R., Venkataraman, P., Vallishayee, R. S., Reeser, P., Musa, S., Hashim, R., Dimmer, C., Wiegeshaus, E., Edwards, M., and Smith, D. W., 1987, Virulence for guinea pigs of tubercle bacilli isolated from the sputum of persons included in the BCG trial, Chingleput district, south India, Tubercle 68:3–17.Google Scholar
  7. 7.
    Tuberculosis Prevention Trial, Madras, 1980, Trial of BCG vaccines in south India for tuberculosis prevention, Indian J. Med. Res. 72(suppl.):l-74.Google Scholar
  8. 8.
    Raleigh, J. W., Wichelhausen, R. H., Rado, T. A., and Bates, J. H., 1975, Evidence for infection by two distinct strains of Mycobacterium tuberculosis in pulmonary tuberculosis: report of nine cases, Am. Rev. Respir. Dis. 112:497–503.PubMedGoogle Scholar
  9. 9.
    Nardell, E., Mclnnis, B., Thomas, B., and Weidhaas, S., 1986, Exogenous reinfection with tuberculosis in a shelter for the homeless, N. Engl. J. Med. 313:1570–1575.CrossRefGoogle Scholar
  10. 10.
    ten Dam, H. G., 1984, Research on BCG vaccination, Adv. Tuberc. Res. 21:79–106.PubMedGoogle Scholar
  11. 11.
    ten Dam, H. G., Toman, K., Hitze. K. L., and Guld, J., 1976, Present knowledge of immunization against tuberculosis, Bull. WHO 54:255–269.PubMedGoogle Scholar
  12. 12.
    Eickhoff, T. C., 1977, The current status of BCG immunization against tuberculosis, Annu. Rev. Med. 28:411–423.PubMedCrossRefGoogle Scholar
  13. 13.
    Aronson, J. D., Aronson, C. F., and Taylor, H. C., 1958, A twenty-year appraisal of BCG vaccination in the control of tuberculosis, AMA Arch. Intern. Med. 101:881–893.PubMedCrossRefGoogle Scholar
  14. 14.
    Hart, P. D., and Sutherland, I. ,1977, BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life. Final report to the Medical Research Council, Br. Med. J. 12:293–295.CrossRefGoogle Scholar
  15. 15.
    Tuberculosis Vaccines Clinical Trials Committee, 1959, BCG and Vole bacillus vaccines in the prevention of tuberculosis in adolescents. Second report to the Medical Research Council, Br. Med. J. 12:379–396.Google Scholar
  16. 16.
    Tuberculosis Prevention Trial, 1979, Trial of BCG vaccines in south India for tuberculosis prevention: first report, Bull. WHO 57:819–827.Google Scholar
  17. 17.
    Tripathy, S. P., 1983, The case for BCG, Ann. Natl. Med. Sci. (India) 19:11–21.Google Scholar
  18. 18.
    Tripathy, S. P., 1986, The Chingleput trial-A 15 year report. Presented at the XXVIth World Conference of the International Union Against Tuberculosis, Singapore, November, 1986.Google Scholar
  19. 19.
    Rosenthal, S. R., 1972, Methods of BCG vaccination, Fogarty Int. Ctr. Proc. 14:179–190.Google Scholar
  20. 20.
    Palmer, C. E., Shaw, L. W., and Comstock, G. W., 1958, Community trials of BCG vaccination, Am. Rev. Tuberc. Respir. Dis. 77:877–907.Google Scholar
  21. 21.
    Comstock, G. W., and Palmer, C. E., 1966, Long-term results of BCG vaccination in the southern United States, Am. Rev. Respir. Dis. 93: 171–183.PubMedGoogle Scholar
  22. 22.
    Comstock, G. W., and Webster, R. G., 1969, Tuberculosis studies in Muscogee County, Georgia. VII. A twenty-year evaluation of BCG vaccination in a school population, Am. Rev. Respir. Dis. 100:839–845.PubMedGoogle Scholar
  23. 23.
    Jespersen, A., and Weis-Bentzon, M., 1967, Relationship between tuberculin sensitivity and acquired resistance in guinea pigs vaccinated with BCG strains of different virulence, Acta Pathol. Microbiol. Scand. 71: 114–131.CrossRefGoogle Scholar
  24. 24.
    Dubos, R. J., and Pierce, C. H., 1956, Differential characteristics in vitro and in vivo of several substrains of BCG. IV. Immunizing effectiveness, Am. Rev. Tuberc. 74:699–717.PubMedGoogle Scholar
  25. 25.
    ICMR/WHO Scientific group, 1980, Vaccination against tuberculosis, WHO Tech. Rep. Ser. 651:1–21.Google Scholar
  26. 26.
    Palmer, C. E., and Long, M. W., 1966, Effects of infection with atypical mycobacteria on BCG-vaccination and tuberculosis, Am. Rev. Respir. Dis. 94:553–568.PubMedGoogle Scholar
  27. 27.
    Edwards, M. L., Goodrich, J. M., Muller, D., Pollack, A., Ziegler, J. E., and Smith, D. W., 1982, Infection with Mycobacterium avium-intracellulare and the protective effects of Bacille Calmette Guerin, J. Infect. Dis. 145:733–741.PubMedCrossRefGoogle Scholar
  28. 28.
    Stanford, J. L.. Shield, M. J., and Rook, G. A., 1981, How environmental mycobacteria may predetermine the protective efficacy of BCG. Hypothesis 1, Tubercle 62:55– 62.PubMedCrossRefGoogle Scholar
  29. 29.
    Comstock, G. W.. and Edwards, P. Q., 1972, An American view of BCG vaccination, illustrated by results of a controlled trial in Puerto Rico, Scand. J. Respir. Dis. 53:207– 217.PubMedGoogle Scholar
  30. 30.
    Smith, D. W., Fok, J. S., Ho, R. S., Harding, G. E., Wiegeshaus, E., and Arora, P. K., 1975, Influence of BCG vaccination on the pathogenesis of experimental airborne tuberculosis, J. Hyg. Epidemiol. Microbiol. Immunol. 19:407–417.PubMedGoogle Scholar
  31. 31.
    Mitchison, D. A., 1964, The virulence of tubercle bacilli from patients with pulmonary tuberculosis in India and other countries, Bull. Int. Union Tuberc. 35:287–306.PubMedGoogle Scholar
  32. 32.
    Naganathan, N., Mahadev, B., Challu, V. K., Rajalakshmi, R., Jones, B., and Smith, D. W., 1986, Virulence of tubercle bacilli isolated from patients with tuberculosis in Bangalore, India, Tubercle 67:261–267.CrossRefGoogle Scholar
  33. 33.
    ten Dam, H. G., and Pio, A.. 1982, Pathogenesis of tuberculosis and the effectiveness of BCG vaccination, Tubercle 63:225–233.PubMedCrossRefGoogle Scholar
  34. 34.
    Ladefoged, A., Bunch-Christensen, K., and Guld, J., 1970, The protective effect in bank voles of some strains of BCG, Bull. WHO 53:435–443.Google Scholar
  35. 35.
    Crowle, A. J., and May, M., 1981, Preliminary demonstration of human tuberculoim-munity in vitro, Infect. Immunol. 31:453–464.Google Scholar
  36. 36.
    Frappier, A., Portelance, V., St. Pierre, J., and Pannisset, M., 1972, BCG strains: Characteristics and relative efficacy, Fogarty Int. Ctr. Proc. 14: 157–178.Google Scholar
  37. 37.
    Smith, D. W., Grover, A. A., and Wiegeshaus, E., 1968, Nonliving immunogenic substances of mycobacteria, Adv. Tuberc. Res. 16:191–227.Google Scholar
  38. 38.
    Smith, D. W., 1985, Protective effect of BCG in experimental tuberculosis Adv. Tuberc. Res. 22:1–97.PubMedGoogle Scholar
  39. 39.
    Crowle, A. J., 1961, Tubercle bacillary extracts immunogenic for mice. 2. Water-soluble proteinaceous extracts, Tubercle 42:479–486.PubMedCrossRefGoogle Scholar
  40. 40.
    Youmans, G. P., and Youmans, A. S., 1957, The measurement of the response of immunized mice to infection with M. tuberculosis var. hominis, J. Immunol. ,78:318–329.PubMedGoogle Scholar
  41. 41.
    Ribi, E., Anacker, R. L., Brehmer, W., Goode, G., Larson, C. L., List, R. H., Milner, K. C., and Wicht, W. C., 1966, Factors influencing protection against experimental tuberculosis in mice by heat-stable cell wall vaccines, J. Bacteriol. 92:869–879.PubMedGoogle Scholar
  42. 42.
    Smith, D. W., Fregnan, G. B., Delaquerriere-Richardson, L., and Valdivia, E., 1964, Induction of acquired resistance in guinea pigs with defatted M. tuberculosis vaccines, J. Bacteriol. 88:87–92.PubMedGoogle Scholar
  43. 43.
    Smith, D. W., Wiegeshaus, E. H., Stark, R. H., and Harding, G. E., 1972, Models for potency assay of tuberculosis vaccines, Fogarty Int. Ctr. Proc. 14:205–218.Google Scholar
  44. 44.
    Smith, D. W., Harding, G. E., Wiegeshaus, E. H., Grover, A. A. ,and McMurray, D. N., 1970, Variables in tuberculosis vaccines test systems; a preliminary report, Symp. Ser. Immunobiol. Std. 17:259–268.Google Scholar
  45. 45.
    Smith, D. W., and Harding, G. E., 1977, Approaches to the validation of animal test systems for assay of protective potency of BCG vaccines, J. Biol. Std. 5: 131–138.CrossRefGoogle Scholar
  46. 46.
    Ribi, E., Anacker, R. L., Barclay, W. R., Brehmer, W., Harris, S. C., Lief, W. R., Simmons, J. ,and Smith, A. W., 1971, Efficacy of mycobacterial cell walls as a vaccine against airborne tuberculosis in the rhesus monkey, J. Infect. Dis. 123:527–538.PubMedCrossRefGoogle Scholar
  47. 47.
    Anacker, R. L. ,Brehmer, W., Barclay, W. R., Leif, W. R., Ribi, E., and Simons, J. H.,1972, Superiority of intravenously administered BCG cell walls in protecting rhesus monkeys (Macaca mulatto) against airborne tuberculosis, Z. Immun.forsch. 143:363–376.Google Scholar
  48. 48.
    Barclay, W. R., Busey, W. M., Dalgard, D. W.. Good, R. C., Janicki, B. W., Kasik, J. E., Ribi, E., Ulrich, C. E., and Wolinsky, E., 1973, Protection of monkeys against airborne tuberculosis by aerosol vaccination with bacillus Calmette-Guerin, Am. Rev. Respir. Dis. 107:351–358.PubMedGoogle Scholar
  49. 49.
    Good, R. C., and McCarroll, N. E., 1977, BCG vaccination in rhesus monkeys: study of skin hypersensitivity and duration of protective immunity, in: Mycobacterial Infections of Zoo Animals (R. J. Montali, ed.), pp. 115–121, Smithsonian Institution Press, Washington, D.C.Google Scholar
  50. 50.
    Ribi, E., Larson, C., Wicht, W., List, R., and Goode, G., 1966, Effective nonliving vaccine against experimental tuberculosis in mice, J. Bacteriol. 91:975–983.PubMedGoogle Scholar
  51. 51.
    Ribi, E., Meyer, T. J. ,Azuma, I. ,Parker, R., and Brehmer, W., 1975, Biologically active components from mycobacterial cell walls. IV. Protection of mice against aerosol infection with virulent Mycobacterium tuberculosis, Cell Immunol. 16:1–10.PubMedCrossRefGoogle Scholar
  52. 52.
    Smith, D. W., Wiegeshaus, E., Navalkar, R., and Grover, A. A., 1966, Host-parasite relationships in experimental airborne tuberculosis. I. Preliminary studies in BCG-vaccinated and nonvaccinated animals, J. Bacteriol. 91:718–724.PubMedGoogle Scholar
  53. 53.
    Schell, R. F., Ealey, W. F., Harding, G. E., and Smith, D. W., 1974, The influence of vaccination on the course of experimental airborne tuberculosis in mice, J. Reticuloendothelial Soc. 16:131–138.Google Scholar
  54. 54.
    Anacker, R. L., Barclay, W. R., Brehmer, W., Goode, G., List, R. H., Ribi, E., and Tarmina, D. F., 1969, Effectiveness of cell walls of Mycobacterium bovis strain BCG administered by various routes and in different adjuvants in protecting mice against airborne infection with Mycobacterium tuberculosis strain H37Rv, Am. Rev. Respir. Dis. 99:242–248.PubMedGoogle Scholar
  55. 55.
    Lefford, M. J. ,1977, Induction and expression of immunity after BCG immunization, Infect. Immun. 18:646–653.PubMedGoogle Scholar
  56. 56.
    Lefford, M. J., 1978, Immunization of mice after airborne infection with various strains of BCG, Am. Rev. Respir. Dis. 117:103–109.PubMedGoogle Scholar
  57. 57.
    Hank, J. A., Chan, J. K., Edwards, M. L., Muller, D., and Smith, D. W., 1981, Influence of the virulence of Mycobacterium tuberculosis on protection induced by bacille Calmette-Guerin in guinea pigs, J. Infect. Dis. 143:734–738.PubMedCrossRefGoogle Scholar
  58. 58.
    Collins, F. M. ,1985, Protection to mice afforded by BCG vaccines against an aerogenic challenge by three mycobacteria of decreasing virulence, Tubercle 66:267–276.PubMedCrossRefGoogle Scholar
  59. 59.
    Wallace, J. G., Mitchison, D. A. ,Rees, R. J. W., Bhatia. A. L., and Gangadharam, P. R. J. ,1961, The virulence of south Indian tubercle bacilli in mice and guinea pigs infected by the intravenous route, Tubercle 42:212–217.PubMedCrossRefGoogle Scholar
  60. 60.
    Orme, I. M. ,Roberts, A. R., and Collins, F. M. ,1986, Lack of evidence for a reduction in the efficacy of subcutaneous BCG vaccination in mice infected with nontuberculous mycobacteria, Tubercle 67:41–46.PubMedCrossRefGoogle Scholar
  61. 61.
    Grover, A. A. ,Kim, H. K., Wiegeshaus, E. H., and Smith, D. W., 1967, Host-parasite relationships in experimental airborne tuberculosis. II. Reproducible infection by means of an inoculum preserved at -70°C, J. Bacteriol. 94:832–835.PubMedGoogle Scholar
  62. 62.
    Wiegeshaus, E. H., McMurray, D. N., Grover, A. A. ,Harding, G. E., and Smith, D. W., 1970, Host-parasite relationships in experimental airborne tuberculosis. III. Relevance of microbial enumeration to acquired resistance in guinea pigs, Am. Rev. Respir. Dis. 102:422–429.PubMedGoogle Scholar
  63. 63.
    Ho, R. S., Fok, J. S., Harding, G. E., and Smith, D. W., 1978, Host-parasite relationships in experimental airborne tuberculosis. VII. Fate of Mycobacterium tuberculosis in primary lung lesions and in primary lesion-free lung tissue infected as a result of bacillemia, J. Infect. Dis. 138:237–241.PubMedCrossRefGoogle Scholar
  64. 64.
    Smith, D. W., McMurray, D. N., Wiegeshaus, E. H., Grover, A. A., and Harding, G. E., 1970, 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. 102:937–949.PubMedGoogle Scholar
  65. 65.
    Mackaness, G. B., 1964, The immunological basis of acquired cellular resistance, J. Exp. Med. 120:105–120.PubMedCrossRefGoogle Scholar
  66. 66.
    Chan, J. K., 1977, Site of control of hematogenous seeding to the lungs in experimental airborne tuberculosis in guinea pigs, Ph.D. thesis, University of Wisconsin, Madison, Wisconsin.Google Scholar
  67. 67.
    Fok, J. S., Ho, R. S., Arora, P. K., Harding, G. E., and Smith, D. W., 1976, 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. 133:137–144.PubMedCrossRefGoogle Scholar
  68. 68.
    Harding, G. E., and Smith, D. W., 1977, Host-parasite relationships in experimental airborne tuberculosis. VI. Influence of vaccination with bacille Calmette-Guérin on the onset and/or extent of hematogenous dissemination of virulent Mycobacterium tuberculosis to the lungs, J. Infect. Dis. 136:439–443.PubMedCrossRefGoogle Scholar
  69. 69.
    McMurray, D. N., Mintzer, C. L., Tetzlaff, C. L., and Carlomagno, M. A., 1986, The influence of dietary protein on the protective effect of BCG in guinea pigs, Tubercle 67:31–39.PubMedCrossRefGoogle Scholar
  70. 70.
    Cohen, M. K., Bartow, R. A., Mintzer, C. A. ,and McMurray, D. N., 1987, Effects of diet and genetics on Mycobacterium bovis BCG vaccine efficacy in inbred guinea pigs, Infect. Immun. 55:314–319.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Donald W. Smith
    • 1
  • Ernst H. Wiegeshaus
    • 1
  • Mark L. Edwards
    • 1
  1. 1.Department of Medical MicrobiologyUniversity of Wisconsin-MadisonMadisonUSA

Personalised recommendations