Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 May;63(5):2004–2011. doi: 10.1128/iai.63.5.2004-2011.1995

Oral immunization with recombinant Salmonella typhimurium expressing surface protein antigen A of Streptococcus sobrinus: dose response and induction of protective humoral responses in rats.

T K Redman 1, C C Harmon 1, R L Lallone 1, S M Michalek 1
PMCID: PMC173257  PMID: 7729915

Abstract

An attenuated, recombinant Salmonella typhimurium mutant, chi 4072(pYA2905), expressing the surface protein antigen A (SpaA) of Streptococcus sobrinus was investigated for its effectiveness in inducing protective immune responses against S. sobrinus-induced dental caries in an experimental caries model. Fischer rats were orally immunized with either 10(8) or 10(9) CFU of S. typhimurium chi 4072(pYA2905). Persistence of salmonellae in Peyer's patches and spleens and the induction of immune responses were determined. Maximum numbers of salmonellae were recovered from Peyer's patches of rats within the first week of immunization, with higher numbers recovered from rats given 10(9) CFU than from those given 10(8) CFU. Serum anti-Salmonella and anti-SpaA responses increased more rapidly in rats given 10(9) CFU than in rats given 10(8) CFU. The salivary antibody response to SpaA increased with time, but the response varied in the two groups. In a separate study, rats were orally immunized with the recombinant Salmonella mutant and then challenged with cariogenic S. sobrinus 6715. The levels of serum and salivary antibody and caries activity were assessed at the termination of the experiment. Higher levels of salivary immunoglobulin A antibody to SpaA and Salmonella carrier were detected in rats given 10(9) CFU than in those given 10(8) CFU, and these responses were higher than those in nonimmunized controls. Mandibular molars from immunized rats had lower numbers of recoverable streptococci and less extensive carious lesions than those from nonimmunized, control rats. These data indicate that oral immunization with an attenuated recombinant S. typhimurium expressing SpaA of S. sobrinus induces the production of antigen-specific mucosal antibody and confers protection against dental caries.

Full Text

The Full Text of this article is available as a PDF (253.0 KB).

Selected References

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

  1. Blancou J., Kieny M. P., Lathe R., Lecocq J. P., Pastoret P. P., Soulebot J. P., Desmettre P. Oral vaccination of the fox against rabies using a live recombinant vaccinia virus. Nature. 1986 Jul 24;322(6077):373–375. doi: 10.1038/322373a0. [DOI] [PubMed] [Google Scholar]
  2. Cao Y., Wen Z., Lu D. Construction of a recombinant oral vaccine against Salmonella typhi and Salmonella typhimurium. Infect Immun. 1992 Jul;60(7):2823–2827. doi: 10.1128/iai.60.7.2823-2827.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carter P. B., Collins F. M. The route of enteric infection in normal mice. J Exp Med. 1974 May 1;139(5):1189–1203. doi: 10.1084/jem.139.5.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chapman P. B., Lonberg M., Houghton A. N. Light chain variants of an IgG3 anti-GD3 monoclonal antibody and the relationship among avidity, effector functions, tumor targeting, and antitumor activity. Cancer Res. 1990 Mar 1;50(5):1503–1509. [PubMed] [Google Scholar]
  5. Connell N., Stover C. K., Jacobs W. R., Jr Old microbes with new faces: molecular biology and the design of new vaccines. Curr Opin Immunol. 1992 Aug;4(4):442–448. doi: 10.1016/s0952-7915(06)80036-1. [DOI] [PubMed] [Google Scholar]
  6. Curtiss R., 3rd, Goldschmidt R. M., Fletchall N. B., Kelly S. M. Avirulent Salmonella typhimurium delta cya delta crp oral vaccine strains expressing a streptococcal colonization and virulence antigen. Vaccine. 1988 Apr;6(2):155–160. doi: 10.1016/s0264-410x(88)80020-3. [DOI] [PubMed] [Google Scholar]
  7. Curtiss R., 3rd, Kelly S. M., Gulig P. A., Nakayama K. Selective delivery of antigens by recombinant bacteria. Curr Top Microbiol Immunol. 1989;146:35–49. doi: 10.1007/978-3-642-74529-4_4. [DOI] [PubMed] [Google Scholar]
  8. Curtiss R., 3rd, Kelly S. M. Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic. Infect Immun. 1987 Dec;55(12):3035–3043. doi: 10.1128/iai.55.12.3035-3043.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Czerkinsky C., Russell M. W., Lycke N., Lindblad M., Holmgren J. Oral administration of a streptococcal antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramucosal tissues. Infect Immun. 1989 Apr;57(4):1072–1077. doi: 10.1128/iai.57.4.1072-1077.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cárdenas L., Clements J. D. Oral immunization using live attenuated Salmonella spp. as carriers of foreign antigens. Clin Microbiol Rev. 1992 Jul;5(3):328–342. doi: 10.1128/cmr.5.3.328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Doggett T. A., Jagusztyn-Krynicka E. K., Curtiss R., 3rd Immune responses to Streptococcus sobrinus surface protein antigen A expressed by recombinant Salmonella typhimurium. Infect Immun. 1993 May;61(5):1859–1866. doi: 10.1128/iai.61.5.1859-1866.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dusek D. M., Progulske-Fox A., Brown T. A. Systemic and mucosal immune responses in mice orally immunized with avirulent Salmonella typhimurium expressing a cloned Porphyromonas gingivalis hemagglutinin. Infect Immun. 1994 May;62(5):1652–1657. doi: 10.1128/iai.62.5.1652-1657.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Eldridge J. H., Gilley R. M., Staas J. K., Moldoveanu Z., Meulbroek J. A., Tice T. R. Biodegradable microspheres: vaccine delivery system for oral immunization. Curr Top Microbiol Immunol. 1989;146:59–66. doi: 10.1007/978-3-642-74529-4_6. [DOI] [PubMed] [Google Scholar]
  14. Galán J. E., Nakayama K., Curtiss R., 3rd Cloning and characterization of the asd gene of Salmonella typhimurium: use in stable maintenance of recombinant plasmids in Salmonella vaccine strains. Gene. 1990 Sep 28;94(1):29–35. doi: 10.1016/0378-1119(90)90464-3. [DOI] [PubMed] [Google Scholar]
  15. Gibbons R. J. Adherent interactions which may affect microbial ecology in the mouth. J Dent Res. 1984 Mar;63(3):378–385. doi: 10.1177/00220345840630030401. [DOI] [PubMed] [Google Scholar]
  16. Goldschmidt R. M., Thoren-Gordon M., Curtiss R., 3rd Regions of the Streptococcus sobrinus spaA gene encoding major determinants of antigen I. J Bacteriol. 1990 Jul;172(7):3988–4001. doi: 10.1128/jb.172.7.3988-4001.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hajishengallis G., Nikolova E., Russell M. W. Inhibition of Streptococcus mutans adherence to saliva-coated hydroxyapatite by human secretory immunoglobulin A (S-IgA) antibodies to cell surface protein antigen I/II: reversal by IgA1 protease cleavage. Infect Immun. 1992 Dec;60(12):5057–5064. doi: 10.1128/iai.60.12.5057-5064.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hamada S., Slade H. D. Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol Rev. 1980 Jun;44(2):331–384. doi: 10.1128/mr.44.2.331-384.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jones B. D., Ghori N., Falkow S. Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches. J Exp Med. 1994 Jul 1;180(1):15–23. doi: 10.1084/jem.180.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. KEYES P. H. Dental caries in the molar teeth of rats. II. A method for diagnosing and scoring several types of lesions simultaneously. J Dent Res. 1958 Nov-Dec;37(6):1088–1099. doi: 10.1177/00220345580370060901. [DOI] [PubMed] [Google Scholar]
  21. Katz J., Harmon C. C., Buckner G. P., Richardson G. J., Russell M. W., Michalek S. M. Protective salivary immunoglobulin A responses against Streptococcus mutans infection after intranasal immunization with S. mutans antigen I/II coupled to the B subunit of cholera toxin. Infect Immun. 1993 May;61(5):1964–1971. doi: 10.1128/iai.61.5.1964-1971.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Katz J., Michalek S. M., Curtiss R., 3rd, Harmon C., Richardson G., Mestecky J. Novel oral vaccines: the effectiveness of cloned gene products on inducing secretory immune responses. Adv Exp Med Biol. 1987;216B:1741–1747. [PubMed] [Google Scholar]
  23. Killar L. M., Eisenstein T. K. Immunity to Salmonella typhimurium infection in C3H/HeJ and C3H/HeNCrlBR mice: studies with an aromatic-dependent live S. typhimurium strain as a vaccine. Infect Immun. 1985 Mar;47(3):605–612. doi: 10.1128/iai.47.3.605-612.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kiyono H., Babb J. L., Michalek S. M., McGhee J. R. Cellular basis for elevated IgA responses in C3H/HeJ mice. J Immunol. 1980 Aug;125(2):732–737. [PubMed] [Google Scholar]
  25. Kraehenbuhl J. P., Neutra M. R. Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev. 1992 Oct;72(4):853–879. doi: 10.1152/physrev.1992.72.4.853. [DOI] [PubMed] [Google Scholar]
  26. Kuramitsu H. K. Virulence factors of mutans streptococci: role of molecular genetics. Crit Rev Oral Biol Med. 1993;4(2):159–176. doi: 10.1177/10454411930040020201. [DOI] [PubMed] [Google Scholar]
  27. LaPolla R. J., Haron J. A., Kelly C. G., Taylor W. R., Bohart C., Hendricks M., Pyati J. P., Graff R. T., Ma J. K., Lehner T. Sequence and structural analysis of surface protein antigen I/II (SpaA) of Streptococcus sobrinus. Infect Immun. 1991 Aug;59(8):2677–2685. doi: 10.1128/iai.59.8.2677-2685.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Loesche W. J. Role of Streptococcus mutans in human dental decay. Microbiol Rev. 1986 Dec;50(4):353–380. doi: 10.1128/mr.50.4.353-380.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. McGhee J. R., Mestecky J., Dertzbaugh M. T., Eldridge J. H., Hirasawa M., Kiyono H. The mucosal immune system: from fundamental concepts to vaccine development. Vaccine. 1992;10(2):75–88. doi: 10.1016/0264-410x(92)90021-b. [DOI] [PubMed] [Google Scholar]
  31. McGhee J. R., Mestecky J. In defense of mucosal surfaces. Development of novel vaccines for IgA responses protective at the portals of entry of microbial pathogens. Infect Dis Clin North Am. 1990 Jun;4(2):315–341. [PubMed] [Google Scholar]
  32. Mestecky J., McGhee J. R. Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv Immunol. 1987;40:153–245. doi: 10.1016/s0065-2776(08)60240-0. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Michalek S. M., Childers N. K. Development and outlook for a caries vaccine. Crit Rev Oral Biol Med. 1990;1(1):37–54. doi: 10.1177/10454411900010010401. [DOI] [PubMed] [Google Scholar]
  35. Michalek S. M., Childers N. K., Katz J., Dertzbaugh M., Zhang S., Russell M. W., Macrina F. L., Jackson S., Mestecky J. Liposomes and conjugate vaccines for antigen delivery and induction of mucosal immune responses. Adv Exp Med Biol. 1992;327:191–198. doi: 10.1007/978-1-4615-3410-5_21. [DOI] [PubMed] [Google Scholar]
  36. Michalek S. M., McGhee J. R., Babb J. L. Effective immunity to dental caries: dose-dependent studies of secretory immunity by oral administration of Streptococcus mutans to rats. Infect Immun. 1978 Jan;19(1):217–224. doi: 10.1128/iai.19.1.217-224.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Michalek S. M., McGhee J. R., Navia J. M. Virulence of Streptococcus mutans: a sensitive method for evaluating cariogenicity in young gnotobiotic rats. Infect Immun. 1975 Jul;12(1):69–75. doi: 10.1128/iai.12.1.69-75.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Michalek S. M., McGhee J. R., Shiota T., Devenyns D. Virulence of Streptococcus mutans: cariogenicity of S. mutans in adult gnotobiotic rats. Infect Immun. 1977 Feb;15(2):466–471. doi: 10.1128/iai.15.2.466-471.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Redman T. K., Harmon C. C., Michalek S. M. Oral immunization with recombinant Salmonella typhimurium expressing surface protein antigen A of Streptococcus sobrinus: persistence and induction of humoral responses in rats. Infect Immun. 1994 Aug;62(8):3162–3171. doi: 10.1128/iai.62.8.3162-3171.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Russell M. W. Immunization against dental caries. Curr Opin Dent. 1992 Sep;2:72–80. [PubMed] [Google Scholar]
  41. Russell M. W., Wu H. Y. Distribution, persistence, and recall of serum and salivary antibody responses to peroral immunization with protein antigen I/II of Streptococcus mutans coupled to the cholera toxin B subunit. Infect Immun. 1991 Nov;59(11):4061–4070. doi: 10.1128/iai.59.11.4061-4070.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Schödel F., Kelly S. M., Peterson D. L., Milich D. R., Curtiss R., 3rd Hybrid hepatitis B virus core-pre-S proteins synthesized in avirulent Salmonella typhimurium and Salmonella typhi for oral vaccination. Infect Immun. 1994 May;62(5):1669–1676. doi: 10.1128/iai.62.5.1669-1676.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Stabel T. J., Mayfield J. E., Tabatabai L. B., Wannemuehler M. J. Oral immunization of mice with attenuated Salmonella typhimurium containing a recombinant plasmid which codes for production of a 31-kilodalton protein of Brucella abortus. Infect Immun. 1990 Jul;58(7):2048–2055. doi: 10.1128/iai.58.7.2048-2055.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Stabel T. J., Mayfield J. E., Tabatabai L. B., Wannemuehler M. J. Swine immunity to an attenuated Salmonella typhimurium mutant containing a recombinant plasmid which codes for production of a 31-kilodalton protein of Brucella abortus. Infect Immun. 1991 Sep;59(9):2941–2947. doi: 10.1128/iai.59.9.2941-2947.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Takahashi I., Okahashi N., Sasakawa C., Yoshikawa M., Hamada S., Koga T. Homology between surface protein antigen genes of Streptococcus sobrinus and Streptococcus mutans. FEBS Lett. 1989 Jun 5;249(2):383–388. doi: 10.1016/0014-5793(89)80664-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES