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. 1978 Apr 1;147(4):1007–1017. doi: 10.1084/jem.147.4.1007

Neutralization of meningococcal endotoxin by antibody to core glycolipid

PMCID: PMC2184252  PMID: 418134

Abstract

Antibodies to Escherichia coli J5, a uridine 5'-diphosphate-galactose epimerase-less mutant of E. coli 0111, neutralized meningococcal endotoxemia from all three major capsular serogroups. We chose the dermal necrosis of the local Shwartzman phenomenon and the renal cortical necrosis of the general Shwartzman phenomenon as assays because these are the hallmarks of meningococcemia, and because meningococcal lipopolysaccharide (LPS) is a uniquely potent cause of dermal purpura and necrosis. Meningococcal antisera raised against LPS from MGC A, B, and C also provided good protection against endotoxemia from the homologous capsular groups, but it was inconsistent against the heterologous serogroups. The superiority of J5 antibodies (purified IgG as well as antiserum) is probably due to the fact that J5 LPS contains only the endotoxin core. Consequently, immunization with this mutant stimulates production of antibodies to core LPS without interference by the "0" antigenic determinants of the side chains. These observations indicate that the endotoxin core is the toxic moiety of meningococcal LPS, that the core LPS of meningococcus (MGC) is immunologically similar to enteric LPS, and that the antigenically variable "0" side chains of MGC LPS interfere with antibody production against the common core. They also suggest that antibodies prepared against this E. coli mutant could interrupt the devastating course of meningococcal endotoxemia in man, regardless of the capsular serogroup of the infecting strain.

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Selected References

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  1. Artenstein M. S. Control of meningococcal meningitis with meningococcal vaccines. Yale J Biol Med. 1975 Jul;48(3):197–200. [PMC free article] [PubMed] [Google Scholar]
  2. Braude A. I., Douglas H. Passive immunization against the local Shwartzman reaction. J Immunol. 1972 Feb;108(2):505–512. [PubMed] [Google Scholar]
  3. Davis C. E., Arnold K. Role of meningococcal endotoxin in meningococcal purpura. J Exp Med. 1974 Jul 1;140(1):159–171. doi: 10.1084/jem.140.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Davis C. E., Brown K. R., Douglas H., Tate W. J., 3rd, Braude A. I. Prevention of death from endotoxin with antisera. I. The risk of fatal anaphylaxis to endotoxin. J Immunol. 1969 Mar;102(3):563–572. [PubMed] [Google Scholar]
  5. Davis C. E., Freedman S. D., Douglas H., Braude A. I. Analysis of sugars in bacterial endotoxins by gas-liquid chromatography. Anal Biochem. 1969 Apr 4;28(1):243–256. doi: 10.1016/0003-2697(69)90175-4. [DOI] [PubMed] [Google Scholar]
  6. ELBEIN A. D., HEATH E. C. THE BIOSYNTHESIS OF CELL WALL LIPOPOLYSACCHARIDE IN ESCHERICHIA COLI. I. THE BIOCHEMICAL PROPERTIES OF A URIDINE DIPHOSPHATE GALACTOSE 4-EPIMERASELESS MUTANT. J Biol Chem. 1965 May;240:1919–1925. [PubMed] [Google Scholar]
  7. Eddie D. S., Schulkind M. L., Robbins J. B. The isolation and biologic activities of purified secretory IgA and IgG anti-Salmonella typhimurium "O" antibodies from rabbit intestinal fluid and colostrum. J Immunol. 1971 Jan;106(1):181–190. [PubMed] [Google Scholar]
  8. Frasch C. E., Chapman S. S. Classification of Neisseria meningitidis group B into distinct serotypes. I. Serological typing by a microbactericidal method. Infect Immun. 1972 Jan;5(1):98–102. doi: 10.1128/iai.5.1.98-102.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Frasch C. E., Parkes L., McNelis R. M., Gotschlich E. C. Protection against group B meningococcal disease. I. Comparison of group-specific and type-specific protection in the chick embryo model. J Exp Med. 1976 Aug 1;144(2):319–329. doi: 10.1084/jem.144.2.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Galanos C., Lüderitz O., Westphal O. Preparation and properties of antisera against the lipid-A component of bacterial lipopolysaccharides. Eur J Biochem. 1971 Dec 22;24(1):116–122. doi: 10.1111/j.1432-1033.1971.tb19661.x. [DOI] [PubMed] [Google Scholar]
  11. Goldschneider I., Gotschlich E. C., Artenstein M. S. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969 Jun 1;129(6):1307–1326. doi: 10.1084/jem.129.6.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gotschlich E. C., Goldschneider I., Artenstein M. S. Human immunity to the meningococcus. IV. Immunogenicity of group A and group C meningococcal polysaccharides in human volunteers. J Exp Med. 1969 Jun 1;129(6):1367–1384. doi: 10.1084/jem.129.6.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gotschlich E. C., Liu T. Y., Artenstein M. S. Human immunity to the meningococcus. 3. Preparation and immunochemical properties of the group A, group B, and group C meningococcal polysaccharides. J Exp Med. 1969 Jun 1;129(6):1349–1365. doi: 10.1084/jem.129.6.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lüderitz O., Staub A. M., Westphal O. Immunochemistry of O and R antigens of Salmonella and related Enterobacteriaceae. Bacteriol Rev. 1966 Mar;30(1):192–255. doi: 10.1128/br.30.1.192-255.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. NETER E., WESTPHAL O., LUDERITZ O., GORZYNSKI E. A., EICHENBERGER E. Studies of enterobacterial lipopolysaccharides; effects of heat and chemicals on erythrocyte-modifying, antigenic, toxic and pyrogenic properties. J Immunol. 1956 May;76(5):377–385. [PubMed] [Google Scholar]
  16. WARREN L. The thiobarbituric acid assay of sialic acids. J Biol Chem. 1959 Aug;234(8):1971–1975. [PubMed] [Google Scholar]
  17. Wahdan M. H., Rizk F., el-Akkad A. M., el-Ghoroury A. A., Hablas R., Girgis N. I., Amer A., Boctar W., Sippel J. E., Gotschlich E. C. A controlled field trial of a serogroup A meningococcal polysaccharide vaccine. Bull World Health Organ. 1973 Jun;48(6):667–673. [PMC free article] [PubMed] [Google Scholar]
  18. Wyle F. A., Artenstein M. S., Brandt B. L., Tramont E. C., Kasper D. L., Altieri P. L., Berman S. L., Lowenthal J. P. Immunologic response of man to group B meningococcal polysaccharide vaccines. J Infect Dis. 1972 Nov;126(5):514–521. doi: 10.1093/infdis/126.5.514. [DOI] [PubMed] [Google Scholar]
  19. Ziegler E. J., Douglas H., Sherman J. E., Davis C. E., Braude A. I. Treatment of E. coli and klebsiella bacteremia in agranulocytic animals with antiserum to a UDP-gal epimerase-deficient mutant. J Immunol. 1973 Aug;111(2):433–438. [PubMed] [Google Scholar]
  20. Ziegler E. J., McCutchan J. A., Douglas H., Braude A. I. Prevention of lethal pseudomonas bacteremia with epimerase-deficient E. coli antiserum. Trans Assoc Am Physicians. 1975;88:101–108. [PubMed] [Google Scholar]
  21. Zollinger W. D., Kasper D. L., Veltri B. J., Artenstein M. S. Isolation and characterization of a native cell wall complex from Neisseria meningitidis. Infect Immun. 1972 Nov;6(5):835–851. doi: 10.1128/iai.6.5.835-851.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zollinger W. D., Pennington C. L., Artenstein M. S. Human antibody response to three meningococcal outer membrane antigens: comparison by specific hemagglutination assays. Infect Immun. 1974 Nov;10(5):975–984. doi: 10.1128/iai.10.5.975-984.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]

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