Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1996 Dec;64(12):5263–5268. doi: 10.1128/iai.64.12.5263-5268.1996

Outer membrane protein of Neisseria meningitidis as a mucosal adjuvant for lipopolysaccharide of Brucella melitensis in mouse and guinea pig intranasal immunization models.

L L Van De Verg 1, A B Hartman 1, A K Bhattacharjee 1, B D Tall 1, L Yuan 1, K Sasala 1, T L Hadfield 1, W D Zollinger 1, D L Hoover 1, R L Warren 1
PMCID: PMC174517  PMID: 8945575

Abstract

A mucosal vaccine against brucellosis consisting of the lipopolysaccharide (LPS) of Brucella melitensis complexed with the outer membrane protein (GBOMP) of group B Neisseria meningitidis was tested in small-animal models of intranasal immunization. Mice given two doses of the vaccine developed high levels of immunoglobulin G (IgG) and IgA antibodies specific for B. melitensis LPS in lung lavages and specific IgG and IgA antibody-secreting cells in the lungs and spleen. Similarly, in guinea pigs immunized twice intranasally, IgG and IgA LPS-specific antibodies were detected in lung lavages, and specific antibody-secreting cells were isolated from the spleen and cervical nodes. In mice immunized with LPS only, pulmonary responses consisted mostly of IgM antibodies, while guinea pigs given LPS alone developed local antibody of all three isotypes, but at lower levels compared to animals given the complex vaccine. Both mice and guinea pigs also developed high levels of serum IgG and moderate levels of IgA as a result of intranasal immunization with the complex vaccine. The serum antibodies in both cases were found to cross-react with the LPS of B. abortus, which shares an immunogenic epitope with B. melitensis LPS. In mice given the complex vaccine, there was a prominent serum IgG1 response that was absent in the mice given LPS alone. In conclusion, the N. meningitidis GBOMP was an effective mucosal adjuvant for secretory IgA and IgG responses in the lungs of both mice and guinea pigs. The IgG1 subclass response in mice suggests that GBOMP may have favored a Th2 type of response to the LPS. A vaccine capable of stimulating high levels of antibody at local sites has the potential to protect against brucellae, since these pathogens gain entry to the host via mucosal routes.

Full Text

The Full Text of this article is available as a PDF (330.7 KB).

Selected References

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

  1. Alving C. R. Liposomal vaccines: clinical status and immunological presentation for humoral and cellular immunity. Ann N Y Acad Sci. 1995 May 31;754:143–152. doi: 10.1111/j.1749-6632.1995.tb44447.x. [DOI] [PubMed] [Google Scholar]
  2. Baldwin C. L., Winter A. J. Macrophages and Brucella. Immunol Ser. 1994;60:363–380. [PubMed] [Google Scholar]
  3. Baqar S., Applebee L. A., Bourgeois A. L. Immunogenicity and protective efficacy of a prototype Campylobacter killed whole-cell vaccine in mice. Infect Immun. 1995 Sep;63(9):3731–3735. doi: 10.1128/iai.63.9.3731-3735.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bundle D. R., Cherwonogrodzky J. W., Caroff M., Perry M. B. The lipopolysaccharides of Brucella abortus and B. melitensis. Ann Inst Pasteur Microbiol. 1987 Jan-Feb;138(1):92–98. doi: 10.1016/0769-2609(87)90083-4. [DOI] [PubMed] [Google Scholar]
  5. Bundle D. R., Cherwonogrodzky J. W., Perry M. B. Structural elucidation of the Brucella melitensis M antigen by high-resolution NMR at 500 MHz. Biochemistry. 1987 Dec 29;26(26):8717–8726. doi: 10.1021/bi00400a034. [DOI] [PubMed] [Google Scholar]
  6. Chen K. S., Burlington D. B., Quinnan G. V., Jr Active synthesis of hemagglutinin-specific immunoglobulin A by lung cells of mice that were immunized intragastrically with inactivated influenza virus vaccine. J Virol. 1987 Jul;61(7):2150–2154. doi: 10.1128/jvi.61.7.2150-2154.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cheville N. F., Stevens M. G., Jensen A. E., Tatum F. M., Halling S. M. Immune responses and protection against infection and abortion in cattle experimentally vaccinated with mutant strains of Brucella abortus. Am J Vet Res. 1993 Oct;54(10):1591–1597. [PubMed] [Google Scholar]
  8. Cloeckaert A., Jacques I., de Wergifosse P., Dubray G., Limet J. N. Protection against Brucella melitensis or Brucella abortus in mice with immunoglobulin G (IgG), IgA, and IgM monoclonal antibodies specific for a common epitope shared by the Brucella A and M smooth lipopolysaccharides. Infect Immun. 1992 Jan;60(1):312–315. doi: 10.1128/iai.60.1.312-315.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Donnelly J. J., Deck R. R., Liu M. A. Immunogenicity of a Haemophilus influenzae polysaccharide-Neisseria meningitidis outer membrane protein complex conjugate vaccine. J Immunol. 1990 Nov 1;145(9):3071–3079. [PubMed] [Google Scholar]
  11. Hartman A. B., Van de Verg L. L., Collins H. H., Jr, Tang D. B., Bendiuk N. O., Taylor D. N., Powell C. J. Local immune response and protection in the guinea pig keratoconjunctivitis model following immunization with Shigella vaccines. Infect Immun. 1994 Feb;62(2):412–420. doi: 10.1128/iai.62.2.412-420.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Liu M. A., Friedman A., Oliff A. I., Tai J., Martinez D., Deck R. R., Shieh J. T., Jenkins T. D., Donnelly J. J., Hawe L. A. A vaccine carrier derived from Neisseria meningitidis with mitogenic activity for lymphocytes. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4633–4637. doi: 10.1073/pnas.89.10.4633. [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. MACKANESS G. B. THE IMMUNOLOGICAL BASIS OF ACQUIRED CELLULAR RESISTANCE. J Exp Med. 1964 Jul 1;120:105–120. doi: 10.1084/jem.120.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Oliveira S. C., Splitter G. A. CD8+ type 1 CD44hi CD45 RBlo T lymphocytes control intracellular Brucella abortus infection as demonstrated in major histocompatibility complex class I- and class II-deficient mice. Eur J Immunol. 1995 Sep;25(9):2551–2557. doi: 10.1002/eji.1830250922. [DOI] [PubMed] [Google Scholar]
  16. Orr N., Robin G., Cohen D., Arnon R., Lowell G. H. Immunogenicity and efficacy of oral or intranasal Shigella flexneri 2a and Shigella sonnei proteosome-lipopolysaccharide vaccines in animal models. Infect Immun. 1993 Jun;61(6):2390–2395. doi: 10.1128/iai.61.6.2390-2395.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Phalipon A., Michetti P., Kaufmann M., Cavaillon J. M., Huerre M., Kraehenbuhl J. P., Sansonetti P. J. Protection against invasion of the mouse pulmonary epithelium by a monoclonal IgA directed against Shigella flexneri lipopolysaccharide. Ann N Y Acad Sci. 1994 Aug 15;730:356–358. doi: 10.1111/j.1749-6632.1994.tb44291.x. [DOI] [PubMed] [Google Scholar]
  18. Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  19. Snapper C. M., Paul W. E. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987 May 22;236(4804):944–947. doi: 10.1126/science.3107127. [DOI] [PubMed] [Google Scholar]
  20. Winter A. J., Duncan J. R., Santisteban C. G., Douglas J. T., Adams L. G. Capacity of passively administered antibody to prevent establishment of Brucella abortus infection in mice. Infect Immun. 1989 Nov;57(11):3438–3444. doi: 10.1128/iai.57.11.3438-3444.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Young E. J. Brucellosis: current epidemiology, diagnosis, and management. Curr Clin Top Infect Dis. 1995;15:115–128. [PubMed] [Google Scholar]
  22. Zhan Y., Cheers C. Endogenous gamma interferon mediates resistance to Brucella abortus infection. Infect Immun. 1993 Nov;61(11):4899–4901. doi: 10.1128/iai.61.11.4899-4901.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Zollinger W. D., Mandrell R. E., Griffiss J. M., Altieri P., Berman S. Complex of meningococcal group B polysaccharide and type 2 outer membrane protein immunogenic in man. J Clin Invest. 1979 May;63(5):836–848. doi: 10.1172/JCI109383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. van de Verg L. L., Mallett C. P., Collins H. H., Larsen T., Hammack C., Hale T. L. Antibody and cytokine responses in a mouse pulmonary model of Shigella flexneri serotype 2a infection. Infect Immun. 1995 May;63(5):1947–1954. doi: 10.1128/iai.63.5.1947-1954.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES