Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1987 Dec;55(12):2984–2992. doi: 10.1128/iai.55.12.2984-2992.1987

Immunization of adult hamsters against Clostridium difficile-associated ileocecitis and transfer of protection to infant hamsters.

P H Kim 1, J P Iaconis 1, R D Rolfe 1
PMCID: PMC260017  PMID: 3679541

Abstract

In this investigation, the role of antibodies against Clostridium difficile toxins A and B in protecting hamsters against C. difficile-associated ileocecitis was examined. We also studied the transfer of protection against C. difficile-associated intestinal disease from immunized female hamsters to their infants. Adult female hamsters immunized parenterally with toxoid A or a mixture containing both toxoids A and B were protected against clindamycin-induced C. difficile-associated fatal ileocecitis. On the other hand, hamsters immunized with toxoid B or a broth filtrate from a nontoxigenic strain of C. difficile were not protected against C. difficile-induced ileocecitis. Antibody against the immunizing toxoid could be demonstrated in both the serum and the cecal contents of hamsters. Some infant hamsters from mothers immunized with toxoid A or AB were protected against C. difficile-associated ileocecitis, while infant hamsters from mothers immunized with toxoid B or a nontoxigenic broth filtrate were not protected against disease. Neutralizing antibodies to toxins A and B could be demonstrated in both maternal milk and serum, as well as in infant serum and intestinal contents. Foster-mothering experiments demonstrated that maternal protection of infants against C. difficile-associated ileocecitis was transferred to infant hamsters through breast milk. These results suggest that toxin A may play a more important role in the pathogenesis of C. difficile-associated ileocecitis in hamsters than toxin B. Furthermore, variations in the severity of C. difficile-associated illness in infants and adults may reflect the lack or presence of passively or actively acquired immunity against C. difficile toxins.

Full text

PDF
2984

Selected References

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

  1. Bartlett J. G. Antibiotic-associated pseudomembranous colitis. Rev Infect Dis. 1979 May-Jun;1(3):530–539. doi: 10.1093/clinids/1.3.530. [DOI] [PubMed] [Google Scholar]
  2. Bolton R. P., Tait S. K., Dear P. R., Losowsky M. S. Asymptomatic neonatal colonisation by Clostridium difficile. Arch Dis Child. 1984 May;59(5):466–472. doi: 10.1136/adc.59.5.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  4. Cooperstock M. S., Steffen E., Yolken R., Onderdonk A. Clostridium difficile in normal infants and sudden infant death syndrome: an association with infant formula feeding. Pediatrics. 1982 Jul;70(1):91–95. [PubMed] [Google Scholar]
  5. DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
  6. Donta S. T., Myers M. G. Clostridium difficile toxin in asymptomatic neonates. J Pediatr. 1982 Mar;100(3):431–434. doi: 10.1016/s0022-3476(82)80454-x. [DOI] [PubMed] [Google Scholar]
  7. Ehrich M., Van Tassell R. L., Libby J. M., Wilkins T. D. Production of Clostridium difficile antitoxin. Infect Immun. 1980 Jun;28(3):1041–1043. doi: 10.1128/iai.28.3.1041-1043.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fernie D. S., Thomson R. O., Batty I., Walker P. D. Active and passive immunization to protect against antibiotic associated caecitis in hamsters. Dev Biol Stand. 1983;53:325–332. [PubMed] [Google Scholar]
  9. Fubara E. S., Freter R. Protection against enteric bacterial infection by secretory IgA antibodies. J Immunol. 1973 Aug;111(2):395–403. [PubMed] [Google Scholar]
  10. George W. L., Rolfe R. D., Finegold S. M. Clostridium difficile and its cytotoxin in feces of patients with antimicrobial agent-associated diarrhea and miscellaneous conditions. J Clin Microbiol. 1982 Jun;15(6):1049–1053. doi: 10.1128/jcm.15.6.1049-1053.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. George W. L., Rolfe R. D., Harding G. K., Klein R., Putnam C. W., Finegold S. M. Clostridium difficile and cytotoxin in feces of patients with antimicrobial agent-associated pseudomembranous colitis. Infection. 1982;10(4):205–208. doi: 10.1007/BF01666910. [DOI] [PubMed] [Google Scholar]
  12. George W. L., Sutter V. L., Citron D., Finegold S. M. Selective and differential medium for isolation of Clostridium difficile. J Clin Microbiol. 1979 Feb;9(2):214–219. doi: 10.1128/jcm.9.2.214-219.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gilligan P. H., McCarthy L. R., Genta V. M. Relative frequency of Clostridium difficile in patients with diarrheal disease. J Clin Microbiol. 1981 Jul;14(1):26–31. doi: 10.1128/jcm.14.1.26-31.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Glass R. I., Svennerholm A. M., Stoll B. J., Khan M. R., Hossain K. M., Huq M. I., Holmgren J. Protection against cholera in breast-fed children by antibodies in breast milk. N Engl J Med. 1983 Jun 9;308(23):1389–1392. doi: 10.1056/NEJM198306093082304. [DOI] [PubMed] [Google Scholar]
  15. Goldman A. S., Smith C. W. Host resistance factors in human milk. J Pediatr. 1973 Jun;82(6):1082–1090. doi: 10.1016/s0022-3476(73)80453-6. [DOI] [PubMed] [Google Scholar]
  16. Holst E., Helin I., Mårdh P. A. Recovery of Clostridium difficile from children. Scand J Infect Dis. 1981;13(1):41–45. doi: 10.1080/00365548.1981.11690365. [DOI] [PubMed] [Google Scholar]
  17. Kim K., DuPont H. L., Pickering L. K. Outbreaks of diarrhea associated with Clostridium difficile and its toxin in day-care centers: evidence of person-to-person spread. J Pediatr. 1983 Mar;102(3):376–382. doi: 10.1016/s0022-3476(83)80652-0. [DOI] [PubMed] [Google Scholar]
  18. Laughon B. E., Viscidi R. P., Gdovin S. L., Yolken R. H., Bartlett J. G. Enzyme immunoassays for detection of Clostridium difficile toxins A and B in fecal specimens. J Infect Dis. 1984 May;149(5):781–788. doi: 10.1093/infdis/149.5.781. [DOI] [PubMed] [Google Scholar]
  19. Lecce J. G., Broughton C. W. Cessation of uptake of macromolecules by neonatal guinea pig, hamster and rabbit intestinal epithelium (closure) and transport into blood. J Nutr. 1973 May;103(5):744–750. doi: 10.1093/jn/103.5.744. [DOI] [PubMed] [Google Scholar]
  20. Libby J. M., Jortner B. S., Wilkins T. D. Effects of the two toxins of Clostridium difficile in antibiotic-associated cecitis in hamsters. Infect Immun. 1982 May;36(2):822–829. doi: 10.1128/iai.36.2.822-829.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lyerly D. M., Saum K. E., MacDonald D. K., Wilkins T. D. Effects of Clostridium difficile toxins given intragastrically to animals. Infect Immun. 1985 Feb;47(2):349–352. doi: 10.1128/iai.47.2.349-352.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Michael J. G., Ringenback R., Hottenstein S. The antimicrobial activity of human colostral antibody in the newborn. J Infect Dis. 1971 Nov;124(5):445–448. doi: 10.1093/infdis/124.5.445. [DOI] [PubMed] [Google Scholar]
  23. Rolfe R. D., Finegold S. M. Purification and characterization of Clostridium difficile toxin. Infect Immun. 1979 Jul;25(1):191–201. doi: 10.1128/iai.25.1.191-201.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rolfe R. D., Iaconis J. P. Intestinal colonization of infant hamsters with Clostridium difficile. Infect Immun. 1983 Nov;42(2):480–486. doi: 10.1128/iai.42.2.480-486.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stark P. L., Lee A., Parsonage B. D. Colonization of the large bowel by Clostridium difficile in healthy infants: quantitative study. Infect Immun. 1982 Mar;35(3):895–899. doi: 10.1128/iai.35.3.895-899.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sullivan N. M., Pellett S., Wilkins T. D. Purification and characterization of toxins A and B of Clostridium difficile. Infect Immun. 1982 Mar;35(3):1032–1040. doi: 10.1128/iai.35.3.1032-1040.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sullivan N. M., Pellett S., Wilkins T. D. Purification and characterization of toxins A and B of Clostridium difficile. Infect Immun. 1982 Mar;35(3):1032–1040. doi: 10.1128/iai.35.3.1032-1040.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Taylor N. S., Thorne G. M., Bartlett J. G. Comparison of two toxins produced by Clostridium difficile. Infect Immun. 1981 Dec;34(3):1036–1043. doi: 10.1128/iai.34.3.1036-1043.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Viscidi R., Laughon B. E., Yolken R., Bo-Linn P., Moench T., Ryder R. W., Bartlett J. G. Serum antibody response to toxins A and B of Clostridium difficile. J Infect Dis. 1983 Jul;148(1):93–100. doi: 10.1093/infdis/148.1.93. [DOI] [PubMed] [Google Scholar]
  30. Viscidi R., Willey S., Bartlett J. G. Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology. 1981 Jul;81(1):5–9. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES