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. 1959 Nov 30;110(6):981–1004. doi: 10.1084/jem.110.6.981

STUDIES ON FRACTIONS OF METHANOL EXTRACTS OF TUBERCLE BACILLI

I. FRACTIONS WHICH INCREASE RESISTANCE TO INFECTION

Curtis A Williams Jr 1, Rene J Dubos 1
PMCID: PMC2137037  PMID: 13844822

Abstract

Fractionation procedures yielding partially purified vaccine preparations from a 60°C. methanol extract of tubercle bacilli have been described. Some of the preparations have the characteristics of lipopolysaccharides. Certain ones have been found capable of increasing resistance to experimental tuberculosis in albino mice of the Rockefeller Swiss strain. The levels of resistance elicited by these preparations are equivalent to those following vaccination with BCG (Phipps) in this strain of mice as reported by other authors. The admixture of two of the crude fractions in amounts as small as 0.05 mg. each per dose per mouse affords an even greater increase in resistance. Neither of these substances alone in larger doses can approach this degree of efficacy in mouse protection experiments. The protective activity appears to involve the stimulation of two supplementary mechanisms, one providing a peak resistance between 1 and 3 weeks post vaccination but falling off to a lower level thereafter, the other not responding fully until approximately 6 weeks but continuing undiminished through a 12 week post-vaccination period. The first of these peaks corresponds to an increase in resistance against staphylococci as well as tubercle bacilli. The possibility that the term "broad specificity," rather than "non-specificity," might best describe this phenomenon permits the implication of classical immune mechanisms.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AEBI A., ASSELINEAU J., LEDERER E. Sur les lipides de la souche humaine Brevannes. de Mycobacterium tuberculosis. Bull Soc Chim Biol (Paris) 1953;35(7):661–684. [PubMed] [Google Scholar]
  2. BLOCH H., SEGAL W. Viability and multiplication of vaccines in immunization against tuberculosis. Am Rev Tuberc. 1955 Feb;71(2):228–248. doi: 10.1164/artpd.1955.71.2.228. [DOI] [PubMed] [Google Scholar]
  3. BOEHME D., DUBOS R. J. The effect of bacterial constituents on the resistance of mice to heterologous infection and on the activity of their reticulo-endothelial system. J Exp Med. 1958 Apr 1;107(4):523–536. doi: 10.1084/jem.107.4.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. CHASE M. W. Experimental sensitization with particular reference to picryl chloride. Int Arch Allergy Appl Immunol. 1954;5(2):163–191. doi: 10.1159/000228095. [DOI] [PubMed] [Google Scholar]
  5. CROWLE A. J. Immunizing constituents of the tubercle bacillus. Bacteriol Rev. 1958 Sep;22(3):183–203. doi: 10.1128/br.22.3.183-203.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DUBOS R. J., SCHAEDLER R. W. Effects of cellular constituents of mycobacteria on the resistance of mice to heterologous infections I. Protective effects. J Exp Med. 1957 Nov 1;106(5):703–717. doi: 10.1084/jem.106.5.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DUBOS R. J., SCHAEFER W. B., PIERCE C. H. Antituberculous immunity in mice vaccinated with killed tubercle bacilli. J Exp Med. 1953 Feb 1;97(2):221–233. doi: 10.1084/jem.97.2.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. ELBERG S. S., FONG J., SCHNEIDER P. Studies on tubercle bacillus-monocyte relationship. I. Quantitative analysis of effect of serum of animals vaccinated with BCG upon bacterium-monocyte system. J Exp Med. 1956 Oct 1;104(4):455–465. doi: 10.1084/jem.104.4.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. ELBERG S. S., SCHNEIDER P., FONG J. Cross-immunity between Brucella melitensis and Mycobacterium tuberculosis; intracellular behavior of Brucella melitensis in monocytes from vaccinated animals. J Exp Med. 1957 Oct 1;106(4):545–554. doi: 10.1084/jem.106.4.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FREUND J., STONE S. H. The effectiveness of tuberculo-glycolipid as an adjuvant in eliciting allergic encephalomyelitis and aspermatogenesis. J Immunol. 1959 Jun;82(6):560–567. [PubMed] [Google Scholar]
  11. LANDY M., PILLEMER L. Increased resistance to infection and accompanying alteration in properidin levels following administration of bacterial lipopolysaccharides. J Exp Med. 1956 Sep 1;104(3):383–409. doi: 10.1084/jem.104.3.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LEVY F. M., CONGE G. Le test de protection de la souris critère d'activité du B. C. G. Rev Immunol Ther Antimicrob. 1955;19(3):210–228. [PubMed] [Google Scholar]
  13. NEGRE L., BRETEY J. Nouvelle preuve expérimentale de l'action immunisante de l'antigène méthylique. Rev Tuberc. 1953;17(10-11):1065–1067. [PubMed] [Google Scholar]
  14. Opie E. L., Freund J. AN EXPERIMENTAL STUDY OF PROTECTIVE INOCULATION WITH HEAT KILLED TUBERCLE BACILLI. J Exp Med. 1937 Nov 30;66(6):761–788. doi: 10.1084/jem.66.6.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. RILEY V. Demonstration of differences between normal and tumor-bearing animals. Proc Soc Exp Biol Med. 1958 Jan;97(1):169–175. doi: 10.3181/00379727-97-23678. [DOI] [PubMed] [Google Scholar]
  16. SMITH J. M., DUBOS R. J. The behavior of virulent and avirulent staphylococci in the tissues of normal mice. J Exp Med. 1956 Jan 1;103(1):87–108. doi: 10.1084/jem.103.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. WEISS D. W., DUBOS R. J. Antituberculous immunity induced by methanol extracts of tubercle bacilli; its enhancement by adjuvants. J Exp Med. 1956 Jan 1;103(1):73–85. doi: 10.1084/jem.103.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. WEISS D. W., DUBOS R. J. Antituberculous immunity induced in mice by vaccination with killed tubercle bacilli or with a soluble bacillary extract. J Exp Med. 1955 Mar 1;101(3):313–330. doi: 10.1084/jem.101.3.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. WHITE R. G., MARSHALL A. H. The role of various chemical fractions of M. tuberculosis and other Mycobacteria in the production of allergic encephalomyelitis. Immunology. 1958 Apr;1(2):111–122. [PMC free article] [PubMed] [Google Scholar]

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