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. 1995 Jul;63(7):2645–2651. doi: 10.1128/iai.63.7.2645-2651.1995

Mucosal immunogenicity of polysaccharides conjugated to a peptide or multiple-antigen peptide containing T- and B-cell epitopes.

E Lett 1, C Klopfenstein 1, J P Klein 1, M Schöller 1, D Wachsmann 1
PMCID: PMC173354  PMID: 7790080

Abstract

In this study we investigated the mucosal and systemic responses to two T-cell-independent polysaccharides, a serogroup f polysaccharide (formed of rhamnose glucose polymers [RGPs]) from Streptococcus mutans OMZ 175 and a mannan from Saccharomyces cerevisiae, covalently conjugated either to a linear peptide (peptide 3) or to a multiple-antigen peptide (MAP), both derived from S. mutans protein SR, an adhesin of the I/II protein antigen family of oral streptococci. Peptide 3 and MAP, which contained at least one B- and one T-cell epitope, were tested as carriers for the polysaccharides and as protective immunogens. Intragastric intubation of rats with the conjugates (RGPs-peptide 3, RGPs-MAP, mannan-peptide 3, and mannan-MAP) associated with liposomes produced salivary immunoglobulin A (IgA) antibodies which reacted with RGPs or mannan, peptide 3 or MAP, protein SR, and S. mutans or S. cerevisiae cells. Administration of conjugate boosters to the animals showed that both carriers conjugated to the polysaccharides were able to induce, in immunized animals, a salivary antipolysaccharide IgA memory. In contrast, animals primed and challenged with unconjugated polysaccharide showed no anamnestic response. Rats orally immunized with the conjugates also developed systemic primary antipolysaccharide and antipeptide IgM antibody responses which were characterized by a switch from IgM to IgG during the course of the secondary response. Data presented here demonstrated that both peptide 3 and the MAP construct can act as good carriers for orally administered polysaccharides. Unexpectedly, the use of a MAP did not further improve the immunogenicity of polysaccharides at the mucosal level; nevertheless, such a construct should be of great interest in overcoming the problem of genetic restriction induced by linear peptides.

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Selected References

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  1. Ackermans F., Pini A., Wachsmann D., Schöller M., Ogier J., Klein J. P. Anti-IgG antibodies in rheumatic diseases cross-react with Streptococcus mutans SR antigen. Clin Exp Immunol. 1991 Aug;85(2):265–269. doi: 10.1111/j.1365-2249.1991.tb05716.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams W. G., Deaver K. A., Cochi S. L., Plikaytis B. D., Zell E. R., Broome C. V., Wenger J. D. Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era. JAMA. 1993 Jan 13;269(2):221–226. [PubMed] [Google Scholar]
  3. Anderson E. L., Bowers T., Mink C. M., Kennedy D. J., Belshe R. B., Harakeh H., Pais L., Holder P., Carlone G. M. Safety and immunogenicity of meningococcal A and C polysaccharide conjugate vaccine in adults. Infect Immun. 1994 Aug;62(8):3391–3395. doi: 10.1128/iai.62.8.3391-3395.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barington T., Gyhrs A., Kristensen K., Heilmann C. Opposite effects of actively and passively acquired immunity to the carrier on responses of human infants to a Haemophilus influenzae type b conjugate vaccine. Infect Immun. 1994 Jan;62(1):9–14. doi: 10.1128/iai.62.1.9-14.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barington T., Skettrup M., Juul L., Heilmann C. Non-epitope-specific suppression of the antibody response to Haemophilus influenzae type b conjugate vaccines by preimmunization with vaccine components. Infect Immun. 1993 Feb;61(2):432–438. doi: 10.1128/iai.61.2.432-438.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Benabdelmoumene S., Dumont S., Petit C., Poindron P., Wachsmann D., Klein J. P. Activation of human monocytes by Streptococcus mutans serotype f polysaccharide: immunoglobulin G Fc receptor expression and tumor necrosis factor and interleukin-1 production. Infect Immun. 1991 Sep;59(9):3261–3266. doi: 10.1128/iai.59.9.3261-3266.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Briand J. P., Barin C., Van Regenmortel M. H., Muller S. Application and limitations of the multiple antigen peptide (MAP) system in the production and evaluation of anti-peptide and anti-protein antibodies. J Immunol Methods. 1992 Dec 8;156(2):255–265. doi: 10.1016/0022-1759(92)90033-p. [DOI] [PubMed] [Google Scholar]
  8. Bruyere T., Wachsmann D., Klein J. P., Schöller M., Frank R. M. Local response in rat to liposome-associated Streptococcus mutans polysaccharide-protein conjugate. Vaccine. 1987 Mar;5(1):39–42. doi: 10.1016/0264-410x(87)90007-7. [DOI] [PubMed] [Google Scholar]
  9. Calvo-Calle J. M., de Oliveira G. A., Clavijo P., Maracic M., Tam J. P., Lu Y. A., Nardin E. H., Nussenzweig R. S., Cochrane A. H. Immunogenicity of multiple antigen peptides containing B and non-repeat T cell epitopes of the circumsporozoite protein of Plasmodium falciparum. J Immunol. 1993 Feb 15;150(4):1403–1412. [PubMed] [Google Scholar]
  10. Carlsson J. Nutritional requirements of Streptococcus sanguis. Arch Oral Biol. 1972 Sep;17(9):1327–1332. doi: 10.1016/0003-9969(72)90165-3. [DOI] [PubMed] [Google Scholar]
  11. Fattom A., Lue C., Szu S. C., Mestecky J., Schiffman G., Bryla D., Vann W. F., Watson D., Kimzey L. M., Robbins J. B. Serum antibody response in adult volunteers elicited by injection of Streptococcus pneumoniae type 12F polysaccharide alone or conjugated to diphtheria toxoid. Infect Immun. 1990 Jul;58(7):2309–2312. doi: 10.1128/iai.58.7.2309-2312.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Francis M. J., Hastings G. Z., Brown F., McDermed J., Lu Y. A., Tam J. P. Immunological evaluation of the multiple antigen peptide (MAP) system using the major immunogenic site of foot-and-mouth disease virus. Immunology. 1991 Jul;73(3):249–254. [PMC free article] [PubMed] [Google Scholar]
  13. Gangloff S., M'Zoughi R., Lett E., Scholler M., Baer J., Pini A., Ogier J., Klein J. P. Epitope mapping of Streptococcus mutans SR protein and human IgG cross-reactive determinants, by using recombinant proteins and synthetic peptides. J Immunol. 1992 May 15;148(10):3249–3255. [PubMed] [Google Scholar]
  14. Jacobs E., Röck R., Dalehite L. A B cell-, T cell-linked epitope located on the adhesin of Mycoplasma pneumoniae. Infect Immun. 1990 Aug;58(8):2464–2469. doi: 10.1128/iai.58.8.2464-2469.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lett E., Gangloff S., Zimmermann M., Wachsmann D., Klein J. P. Immunogenicity of polysaccharides conjugated to peptides containing T- and B-cell epitopes. Infect Immun. 1994 Mar;62(3):785–792. doi: 10.1128/iai.62.3.785-792.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Monsigny M., Petit C., Roche A. C. Colorimetric determination of neutral sugars by a resorcinol sulfuric acid micromethod. Anal Biochem. 1988 Dec;175(2):525–530. doi: 10.1016/0003-2697(88)90578-7. [DOI] [PubMed] [Google Scholar]
  17. Munesinghe D. Y., Clavijo P., Calle M. C., Nussenzweig R. S., Nardin E. Immunogenicity of multiple antigen peptides (MAP) containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite protein. Eur J Immunol. 1991 Dec;21(12):3015–3020. doi: 10.1002/eji.1830211217. [DOI] [PubMed] [Google Scholar]
  18. Nardelli B., Haser P. B., Tam J. P. Oral administration of an antigenic synthetic lipopeptide (MAP-P3C) evokes salivary antibodies and systemic humoral and cellular responses. Vaccine. 1994 Nov;12(14):1335–1339. doi: 10.1016/s0264-410x(94)80062-5. [DOI] [PubMed] [Google Scholar]
  19. Ogier J. A., Pini A., Sommer P., Klein J. P. Purification and characterization of the expression product of the sr gene of Streptococcus mutans OMZ 175. Microb Pathog. 1989 Mar;6(3):175–182. doi: 10.1016/0882-4010(89)90067-3. [DOI] [PubMed] [Google Scholar]
  20. Peeters C. C., Tenbergen-Meekes A. M., Poolman J. T., Beurret M., Zegers B. J., Rijkers G. T. Effect of carrier priming on immunogenicity of saccharide-protein conjugate vaccines. Infect Immun. 1991 Oct;59(10):3504–3510. doi: 10.1128/iai.59.10.3504-3510.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pritchard D. G., Michalek S. M., McGhee J. R., Furner R. L. Structure of the serotype f polysaccharide antigen of Streptococcus mutans. Carbohydr Res. 1987 Aug 15;166(1):123–131. doi: 10.1016/0008-6215(87)80049-6. [DOI] [PubMed] [Google Scholar]
  22. Robbins J. B., Schneerson R. Polysaccharide-protein conjugates: a new generation of vaccines. J Infect Dis. 1990 May;161(5):821–832. doi: 10.1093/infdis/161.5.821. [DOI] [PubMed] [Google Scholar]
  23. Sanderson C. J., Wilson D. V. A simple method for coupling proteins to insoluble polysaccharides. Immunology. 1971 Jun;20(6):1061–1065. [PMC free article] [PubMed] [Google Scholar]
  24. Smith D. J., Taubman M. A., Holmberg C. F., Eastcott J., King W. F., Ali-Salaam P. Antigenicity and immunogenicity of a synthetic peptide derived from a glucan-binding domain of mutans streptococcal glucosyltransferase. Infect Immun. 1993 Jul;61(7):2899–2905. doi: 10.1128/iai.61.7.2899-2905.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Soell M., Lett E., Holveck F., Schöller M., Wachsmann D., Klein J. P. Activation of human monocytes by streptococcal rhamnose glucose polymers is mediated by CD14 antigen, and mannan binding protein inhibits TNF-alpha release. J Immunol. 1995 Jan 15;154(2):851–860. [PubMed] [Google Scholar]
  26. Tam J. P. Synthetic peptide vaccine design: synthesis and properties of a high-density multiple antigenic peptide system. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5409–5413. doi: 10.1073/pnas.85.15.5409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wachsmann D., Klein J. P., Scholler M., Ogier J., Ackermans F., Frank R. M. Serum and salivary antibody responses in rats orally immunized with Streptococcus mutans carbohydrate protein conjugate associated with liposomes. Infect Immun. 1986 May;52(2):408–413. doi: 10.1128/iai.52.2.408-413.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wachsmann D., Klein J. P., Schöller M., Frank R. M. Local and systemic immune response to orally administered liposome-associated soluble S. mutans cell wall antigens. Immunology. 1985 Jan;54(1):189–193. [PMC free article] [PubMed] [Google Scholar]

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