Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1995 Sep;63(9):3279–3286. doi: 10.1128/iai.63.9.3279-3286.1995

A recombinant Salmonella typhimurium vaccine induces local immunity by four different routes of immunization.

S Hopkins 1, J P Kraehenbuhl 1, F Schödel 1, A Potts 1, D Peterson 1, P de Grandi 1, D Nardelli-Haefliger 1
PMCID: PMC173452  PMID: 7642256

Abstract

Immunization of mice with an attenuated Salmonella typhimurium strain (Phopc) carrying a plasmid encoding a hybrid form of the hepatitis B virus core antigen (HBc) induced specific antibody responses against the bacterial lipopolysaccharide (LPS) and HBc. Different mucosal routes of immunization, i.e., oral, nasal, rectal, and vaginal, were compared for their ability to induce a systemic as well as a mucosal response at sites proximal or distant to the site of immunization. Anti-LPS and anti-HBc immunoglobulin A (IgA) antibodies were measured in saliva, in feces, and in genital, bronchial, and intestinal secretions. Specific antibodies in serum and secretions were observed after immunization via all routes; however, the response to LPS was independent of that against HBc. In serum, saliva, and genital and bronchial secretions, high amounts of anti-HBc IgA were obtained by the nasal route of immunization. Vaginal immunization resulted in two different responses in mice: high and low. We observed a correlation between the level of specific immune response and the estrous status of these mice at the time of immunization. Rectal immunization induced high amounts of IgA against HBc and LPS in colonorectal secretions and feces but not at distant sites. These data suggest that S. typhimurium is able to invade different mucosal tissues and induce long-lasting local IgA responses against itself and a carried antigen after a single immunization.

Full Text

The Full Text of this article is available as a PDF (323.6 KB).

Selected References

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

  1. Clark M. A., Jepson M. A., Simmons N. L., Hirst B. H. Preferential interaction of Salmonella typhimurium with mouse Peyer's patch M cells. Res Microbiol. 1994 Sep;145(7):543–552. doi: 10.1016/0923-2508(94)90031-0. [DOI] [PubMed] [Google Scholar]
  2. Curtiss R., 3rd, Nakayama K., Kelly S. M. Recombinant avirulent Salmonella vaccine strains with stable maintenance and high level expression of cloned genes in vivo. Immunol Invest. 1989 Jan-May;18(1-4):583–596. doi: 10.3109/08820138909112265. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Forrest B. D., Shearman D. J., LaBrooy J. T. Specific immune response in humans following rectal delivery of live typhoid vaccine. Vaccine. 1990 Jun;8(3):209–212. doi: 10.1016/0264-410x(90)90047-p. [DOI] [PubMed] [Google Scholar]
  5. Haneberg B., Kendall D., Amerongen H. M., Apter F. M., Kraehenbuhl J. P., Neutra M. R. Induction of specific immunoglobulin A in the small intestine, colon-rectum, and vagina measured by a new method for collection of secretions from local mucosal surfaces. Infect Immun. 1994 Jan;62(1):15–23. doi: 10.1128/iai.62.1.15-23.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Kuper C. F., Koornstra P. J., Hameleers D. M., Biewenga J., Spit B. J., Duijvestijn A. M., van Breda Vriesman P. J., Sminia T. The role of nasopharyngeal lymphoid tissue. Immunol Today. 1992 Jun;13(6):219–224. doi: 10.1016/0167-5699(92)90158-4. [DOI] [PubMed] [Google Scholar]
  9. Langermann S., Palaszynski S., Sadziene A., Stover C. K., Koenig S. Systemic and mucosal immunity induced by BCG vector expressing outer-surface protein A of Borrelia burgdorferi. Nature. 1994 Dec 8;372(6506):552–555. doi: 10.1038/372552a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Milich D. R., McLachlan A., Moriarty A., Thornton G. B. Immune response to hepatitis B virus core antigen (HBcAg): localization of T cell recognition sites within HBcAg/HBeAg. J Immunol. 1987 Aug 15;139(4):1223–1231. [PubMed] [Google Scholar]
  13. Milich D. R., McLachlan A. The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen. Science. 1986 Dec 12;234(4782):1398–1401. doi: 10.1126/science.3491425. [DOI] [PubMed] [Google Scholar]
  14. Miller S. I., Mekalanos J. J. Constitutive expression of the phoP regulon attenuates Salmonella virulence and survival within macrophages. J Bacteriol. 1990 May;172(5):2485–2490. doi: 10.1128/jb.172.5.2485-2490.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Neutra M. R., Kraehenbuhl J. P. Transepithelial transport and mucosal defence I: the role of M cells. Trends Cell Biol. 1992 May;2(5):134–138. doi: 10.1016/0962-8924(92)90099-9. [DOI] [PubMed] [Google Scholar]
  16. Ogra P. L., Ogra S. S. Local antibody response to poliovaccine in the human female genital tract. J Immunol. 1973 May;110(5):1307–1311. [PubMed] [Google Scholar]
  17. Parr M. B., Parr E. L. Antigen recognition in the female reproductive tract: I. Uptake of intraluminal protein tracers in the mouse vagina. J Reprod Immunol. 1990 Apr;17(2):101–114. doi: 10.1016/0165-0378(90)90029-6. [DOI] [PubMed] [Google Scholar]
  18. Schödel F., Enders G., Jung M. C., Will H. Recognition of a hepatitis B virus nucleocapsid T-cell epitope expressed as a fusion protein with the subunit B of Escherichia coli heat labile enterotoxin in attenuated salmonellae. Vaccine. 1990 Dec;8(6):569–572. doi: 10.1016/0264-410x(90)90010-j. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Schödel F., Milich D. R., Will H. Hepatitis B virus nucleocapsid/pre-S2 fusion proteins expressed in attenuated Salmonella for oral vaccination. J Immunol. 1990 Dec 15;145(12):4317–4321. [PubMed] [Google Scholar]
  21. Schödel F. Prospects for oral vaccination using recombinant bacteria expressing viral epitopes. Adv Virus Res. 1992;41:409–446. doi: 10.1016/s0065-3527(08)60041-x. [DOI] [PubMed] [Google Scholar]
  22. Sminia T., van der Brugge-Gamelkoorn G. J., Jeurissen S. H. Structure and function of bronchus-associated lymphoid tissue (BALT). Crit Rev Immunol. 1989;9(2):119–150. [PubMed] [Google Scholar]
  23. Vos J. G., Buys J., Hanstede J. G., Hagenaars A. M. Comparison of enzyme-linked immunosorbent assay and passive hemagglutination method for quantification of antibodies to lipopolysaccharide and tetanus toxoid in rats. Infect Immun. 1979 Jun;24(3):798–803. doi: 10.1128/iai.24.3.798-803.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wu H. Y., Russell M. W. Induction of mucosal immunity by intranasal application of a streptococcal surface protein antigen with the cholera toxin B subunit. Infect Immun. 1993 Jan;61(1):314–322. doi: 10.1128/iai.61.1.314-322.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Young W. G., Newcomb G. M., Hosking A. R. The effect of atrophy, hyperplasia, and keratinization accompanying the estrous cycle on Langerhans' cells in mouse vaginal epithelium. Am J Anat. 1985 Oct;174(2):173–186. doi: 10.1002/aja.1001740207. [DOI] [PubMed] [Google Scholar]

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

RESOURCES