Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1989 Apr;57(4):1072–1077. doi: 10.1128/iai.57.4.1072-1077.1989

Oral administration of a streptococcal antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramucosal tissues.

C Czerkinsky 1, M W Russell 1, N Lycke 1, M Lindblad 1, J Holmgren 1
PMCID: PMC313231  PMID: 2925239

Abstract

Generation of local and systemic immune responses by the oral administration of antigens is frequently inefficient, requiring large quantities of immunogens and yielding only modest antibody responses. In this study, we have demonstrated that oral administration of microgram amounts of Streptococcus mutans protein antigen I/II covalently coupled to the B subunit of cholera toxin elicits vigorous mucosal as well as extramucosal immunoglobulin A and G antistreptococcal antibody responses in mice. These responses were manifested by the presence of large numbers of antibody-secreting cells in salivary glands, mesenteric lymph nodes, and spleens and by the development of high levels of circulating antibodies. This novel immunization strategy may find broad application in the construction of oral vaccines for the control of infectious diseases caused by pathogens encountered at mucosal and extramucosal sites.

Full text

PDF
1072

Selected References

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

  1. Carlsson J., Drevin H., Axén R. Protein thiolation and reversible protein-protein conjugation. N-Succinimidyl 3-(2-pyridyldithio)propionate, a new heterobifunctional reagent. Biochem J. 1978 Sep 1;173(3):723–737. doi: 10.1042/bj1730723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cebra J. J., Gearhart P. J., Kamat R., Robertson S. M., Tseng J. Origin and differentiation of lymphocytes involved in the secretory IgA responses. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):201–215. doi: 10.1101/sqb.1977.041.01.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Czerkinsky C. C., Nilsson L. A., Nygren H., Ouchterlony O., Tarkowski A. A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells. J Immunol Methods. 1983 Dec 16;65(1-2):109–121. doi: 10.1016/0022-1759(83)90308-3. [DOI] [PubMed] [Google Scholar]
  4. Czerkinsky C., Prince S. J., Michalek S. M., Jackson S., Russell M. W., Moldoveanu Z., McGhee J. R., Mestecky J. IgA antibody-producing cells in peripheral blood after antigen ingestion: evidence for a common mucosal immune system in humans. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2449–2453. doi: 10.1073/pnas.84.8.2449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. De Buysscher E. V., Dubois P. R. Detection of IgA anti-Escherichia coli plasma cells in the intestine and salivary glands of pigs orally and locally infected with E. coli. Adv Exp Med Biol. 1978;107:593–600. doi: 10.1007/978-1-4684-3369-2_67. [DOI] [PubMed] [Google Scholar]
  6. Elson C. O., Ealding W. Cholera toxin feeding did not induce oral tolerance in mice and abrogated oral tolerance to an unrelated protein antigen. J Immunol. 1984 Dec;133(6):2892–2897. [PubMed] [Google Scholar]
  7. Goldblum R. M., Ahlstedt S., Carlsson B., Hanson L. A., Jodal U., Lidin-Janson G., Sohl-Akerlund A. Antibody-forming cells in human colostrum after oral immunisation. Nature. 1975 Oct 30;257(5529):797–798. doi: 10.1038/257797a0. [DOI] [PubMed] [Google Scholar]
  8. Holmgren J. Actions of cholera toxin and the prevention and treatment of cholera. Nature. 1981 Jul 30;292(5822):413–417. doi: 10.1038/292413a0. [DOI] [PubMed] [Google Scholar]
  9. Holmgren J., Svennerholm A. M., Lönnroth I., Fall-Persson M., Markman B., Lundbeck H. Development of improved cholera vaccine based on subunit toxoid. Nature. 1977 Oct 13;269(5629):602–604. doi: 10.1038/269602a0. [DOI] [PubMed] [Google Scholar]
  10. Jackson D. E., Lally E. T., Nakamura M. C., Montgomery P. C. Migration of IgA-bearing lymphocytes into salivary glands. Cell Immunol. 1981 Sep 1;63(1):203–209. doi: 10.1016/0008-8749(81)90042-3. [DOI] [PubMed] [Google Scholar]
  11. Lamm M. E. Cellular aspects of immunoglobulin A. Adv Immunol. 1976;22:223–290. doi: 10.1016/s0065-2776(08)60550-7. [DOI] [PubMed] [Google Scholar]
  12. Lehner T., Russell M. W., Caldwell J., Smith R. Immunization with purified protein antigens from Streptococcus mutans against dental caries in rhesus monkeys. Infect Immun. 1981 Nov;34(2):407–415. doi: 10.1128/iai.34.2.407-415.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lycke N., Holmgren J. Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens. Immunology. 1986 Oct;59(2):301–308. [PMC free article] [PubMed] [Google Scholar]
  14. McDermott M. R., Bienenstock J. Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues. J Immunol. 1979 May;122(5):1892–1898. [PubMed] [Google Scholar]
  15. McGhee J. R., Michalek S. M. Immunobiology of dental caries: microbial aspects and local immunity. Annu Rev Microbiol. 1981;35:595–638. doi: 10.1146/annurev.mi.35.100181.003115. [DOI] [PubMed] [Google Scholar]
  16. McGhee, Michalek S. M., Webb J., Navia J. M., Rahman A. F., Legler D. W. Effective immunity to dental caries: protection of gnotobiotic rats by local immunization with Streptococcus mutans. J Immunol. 1975 Jan;114(1 Pt 2):300–305. [PubMed] [Google Scholar]
  17. McKenzie S. J., Halsey J. F. Cholera toxin B subunit as a carrier protein to stimulate a mucosal immune response. J Immunol. 1984 Oct;133(4):1818–1824. [PubMed] [Google Scholar]
  18. Mestecky J., McGhee J. R., Arnold R. R., Michalek S. M., Prince S. J., Babb J. L. Selective induction of an immune response in human external secretions by ingestion of bacterial antigen. J Clin Invest. 1978 Mar;61(3):731–737. doi: 10.1172/JCI108986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mestecky J. The common mucosal immune system and current strategies for induction of immune responses in external secretions. J Clin Immunol. 1987 Jul;7(4):265–276. doi: 10.1007/BF00915547. [DOI] [PubMed] [Google Scholar]
  20. Michalek S. M., McGhee J. R., Mestecky J., Arnold R. R., Bozzo L. Ingestion of Streptococcus mutans induces secretory immunoglobulin A and caries immunity. Science. 1976 Jun 18;192(4245):1238–1240. doi: 10.1126/science.1273589. [DOI] [PubMed] [Google Scholar]
  21. Montgomery P. C., Cohn J., Lally E. T. The induction and characterization of secretory IgA antibodies. Adv Exp Med Biol. 1974;45(0):453–462. doi: 10.1007/978-1-4613-4550-3_54. [DOI] [PubMed] [Google Scholar]
  22. Nedrud J. G., Liang X. P., Hague N., Lamm M. E. Combined oral/nasal immunization protects mice from Sendai virus infection. J Immunol. 1987 Nov 15;139(10):3484–3492. [PubMed] [Google Scholar]
  23. Ogra P. L., Chiba Y., Beutner K. R., Morag A. Vaccination by non-parenteral routes: characteristics of immune response. Dev Biol Stand. 1976;33:19–26. [PubMed] [Google Scholar]
  24. Pierce N. F. The role of antigen form and function in the primary and secondary intestinal immune responses to cholera toxin and toxoid in rats. J Exp Med. 1978 Jul 1;148(1):195–206. doi: 10.1084/jem.148.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Russell M. W., Bergmeier L. A., Zanders E. D., Lehner T. Protein antigens of Streptococcus mutans: purification and properties of a double antigen and its protease-resistant component. Infect Immun. 1980 May;28(2):486–493. doi: 10.1128/iai.28.2.486-493.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Russell M. W., Czerkinsky C., Moldoveanu Z. Detection and specificity of antibodies secreted by spleen cells in mice immunized with Streptococcus mutans. Infect Immun. 1986 Aug;53(2):317–323. doi: 10.1128/iai.53.2.317-323.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sedgwick J. D., Holt P. G. A solid-phase immunoenzymatic technique for the enumeration of specific antibody-secreting cells. J Immunol Methods. 1983 Feb 25;57(1-3):301–309. doi: 10.1016/0022-1759(83)90091-1. [DOI] [PubMed] [Google Scholar]
  28. Svennerholm A. M., Gothefors L., Sack D. A., Bardhan P. K., Holmgren J. Local and systemic antibody responses and immunological memory in humans after immunization with cholera B subunit by different routes. Bull World Health Organ. 1984;62(6):909–918. [PMC free article] [PubMed] [Google Scholar]
  29. Talbman M. A., Smith D. J. Effects of local immunization with Streptococcus mutans on induction of salivary immunoglobulin A antibody and experimental dental caries in rats. Infect Immun. 1974 Jun;9(6):1079–1091. doi: 10.1128/iai.9.6.1079-1091.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Taubman M. A., Smith D. J. A mucosal approach to immunoprophylaxis of dental infections. Adv Exp Med Biol. 1987;216B:1721–1730. [PubMed] [Google Scholar]
  31. Tayot J. L., Holmgren J., Svennerholm L., Lindblad M., Tardy M. Receptor-specific large-scale purification of cholera toxin on silica beads derivatized with lysoGM1 ganglioside. Eur J Biochem. 1981 Jan;113(2):249–258. doi: 10.1111/j.1432-1033.1981.tb05060.x. [DOI] [PubMed] [Google Scholar]
  32. Weisz-Carrington P., Roux M. E., McWilliams M., PHILLIPS-Quagliata J. M., Lamm M. E. Organ and isotype distribution of plasma cells producing specific antibody after oral immunization: evidence for a generalized secretory immune system. J Immunol. 1979 Oct;123(4):1705–1708. [PubMed] [Google Scholar]
  33. de Aizpurua H. J., Russell-Jones G. J. Oral vaccination. Identification of classes of proteins that provoke an immune response upon oral feeding. J Exp Med. 1988 Feb 1;167(2):440–451. doi: 10.1084/jem.167.2.440. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES