The development of a new adjuvant lipid-saponin complex and its use at experimental immunization by bacterial antigen

  • A. V. TsybulskyEmail author
  • N. M. Sanina
  • I. A. Lee
  • A. M. Popov
  • E. Ya. Kostetsky
  • O. Yu. Portnyagina
  • V. L. Shnyrov
Experimental Studies


Immunostimulating complexes (ISCOM) have been modified by replacement of structural components of ISCOM; phosphatidylcholine has been replaced, by glycolipid of monogalactosyldiacylglycerol from sea macrophytes, saponin QuilA has been replaced by triterpene glycoside, Cucumarioside A2-2. The resultant complex includes morphological structures of two types: the ISCOM-like structures with the characteristic morphology and sizes and also the tubular structures with diameter of about 40 nm and length of 150–400 nm. We have defined these structures as TI-complexes. These TI-complexes exhibit considerably lower toxicity than ISCOM. They may include an amphiphilic protein antigen and provide immunoadjuvant effect during experimental vaccination. Under conditions of the experimental immunization of mice with a weak immunogen (subunit membrane pore protein from Y. pseudotuberculosis), TI-complexes with antigen provided stronger humoral immune response to antigen than the complexes of porin with classical ISCOM, liposomes and Freund’s adjuvant. Thus, the TI-complexes represent a new type of adjuvant carriers for antigens.

Key words

adjuvant ISCOM triterpene glycoside monogalactosyldiacylglycerol (MGDG) vaccine porin 


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  1. 1.
    Bomford, R., in Control of Infectious Disease, Dimmock, N.J., Griffiths, P.D., and Madeley, C.R., Eds., Cambridge: Cambridge University Press, 1990, pp. 143–154.Google Scholar
  2. 2.
    Babai, I., Barenholz, Y., Zakay-Rones, Z., Greenbaum, E., Samira, S., Hayon, J., Rochman, M., and Kedar, E., Vaccine, 2001, vol. 20, pp. 505–515.CrossRefGoogle Scholar
  3. 3.
    Lasic, D.D., in Handbook of Biological Physics, vol. 1, Lipowsky, R. and Sackmann, E., Eds., Elsevier Science B.V., 1995, pp. 491–519.Google Scholar
  4. 4.
    Van Slooten, M.L., Boerman, O., Romoren, K., Kedar, E., Grommelin, D.J., and Staorm, G., Biochim. Biophys. Acta, 2001, vol. 1530, pp. 134–145.Google Scholar
  5. 5.
    Morein, B., Lovgren, K., Hoglund, S., and Sundquist, B., Immunol. Today, 1987, vol. 8, pp. 333–338.CrossRefGoogle Scholar
  6. 6.
    Morein, B., Lovgren, K., and Hoglund, S., in Immunological Adjuvants and Vaccines, Gregoriadis, G., Ed., New York: Plenum, 1989, pp. 153–162.Google Scholar
  7. 7.
    Gupta, R.K., Relyverd, E.H., Lindblad, E.B., Bizzini, B., Ben-Efraim, S., and Gupta, C.K., Vaccine, 1993, vol. 11, pp. 293–306.CrossRefGoogle Scholar
  8. 8.
    Mowat, A.M., Donachie, A.M., Reid, G., and Jarrett, O., Immunology, 1991, vol. 72, pp. 317–322.Google Scholar
  9. 9.
    San Gil, F., Turner, B., Mullbacher, A., Walker, M.J., Djorjevich, S.P., Eamens, G.J., and Chin, J.C., Scand. J. Immunol., 1998, vol. 47, pp. 243–253.CrossRefGoogle Scholar
  10. 10.
    Kensil, C.R., Patel, U., Lennick, M., and Marciani, D., J. Immunol., 1991, vol. 146, pp. 431–437.Google Scholar
  11. 11.
    Ronnberg, B., Fekadu, M., Behboudi, S., Kennel, L., and Morein, B., Vaccine, 1997, vol. 15, pp. 1820–1826.CrossRefGoogle Scholar
  12. 12.
    Bruno, A., Rossi, C., Marcolongo, G., Dilena, A., Venzo, A., Berrie, C.P., and Corda, D., Eur. J. Pharmacol., 2005, vol. 524, pp. 159–168.CrossRefGoogle Scholar
  13. 13.
    Sedov, A.M., Apollonin, A.V., Sebast’yanova, E.K., et al., Antibiotiki i Khimioterapiya, 1990, vol. 35, pp. 23–27.Google Scholar
  14. 14.
    Aminin, D.L., Pinegin, B.V., Pichugina, L.V., Zaporozhets, T.S., Agafonova, J.G., Boguslavski, V.M., Silchenko, A.S., Avilov, S.A., and Stonik, V.A., Int. Immunopharmacol., 2006, vol. 6, pp. 1070–1082.CrossRefGoogle Scholar
  15. 15.
    Li, I.A., Popov, A.M., Sanina, N.M., et al., Izvestiya RAN. Ser. Biol., 2004, vol. 3, pp. 299–304.Google Scholar
  16. 16.
    Lee, I.A., Popov, A.M. Sanina, N.M., Kostetsky, E.Y., Novikova, O.D., Reunov, A.V., Nagorskaya, V.P., and Shnyrov, V.L., Acta Biochimica Polonica, 2004, vol. 51, pp. 263–272.Google Scholar
  17. 17.
    Kostetskii, E.Ya, Popov, A.M., Sanina, N.M., et al., Zayavka na patent no. 2006104795/13(005189), 15.02.2006.Google Scholar
  18. 18.
    Singleton, W.S., Gray, M.S., Brown, M.Z., and White, G.Z., J. Am. Oil Chem. Soc., 1965, vol. 42, pp. 53–56.CrossRefGoogle Scholar
  19. 19.
    Sanina, N.M., Goncharova, S.N., and Kostetsky, E.Y., in Advanced Research on Plant Lipids, Murata et al., Eds., Dordrecht: Kluwer Academic Publishers, 2003, pp. 385–388.Google Scholar
  20. 20.
    Portnyagina, O.Yu., Novikova, O.D., Vostrikova, O.P., and Solov’eva, T.F., Byull. Eksper. Biol. Med., 1999, vol. 128, pp. 437–440.Google Scholar
  21. 21.
    Charles, S.D., Nagaraja, K.V., and Sivanandan, V., Avian Dis., 1993, vol. 37, pp. 477–484.CrossRefGoogle Scholar
  22. 22.
    Kalinin, V.I., Levin, V.S., and Stonik, V.A., Khimicheskaya morfologiya: triterpenovye glikozidu goloturii (Chemical Morphology: Triterpene Glycosides from Sea Cucumbers), Vladivostok: Dal’nauka, 1994.Google Scholar

Copyright information

© Pleiades Publishing, Ltd. 2007

Authors and Affiliations

  • A. V. Tsybulsky
    • 1
    Email author
  • N. M. Sanina
    • 1
  • I. A. Lee
    • 2
  • A. M. Popov
    • 2
  • E. Ya. Kostetsky
    • 1
  • O. Yu. Portnyagina
    • 2
  • V. L. Shnyrov
    • 3
  1. 1.Department of Biochemistry and BiotechnologyFar Eastern State UniversityVladivostokRussia
  2. 2.Pacific Institute of Bioorganic ChemistryFar Eastern Branch of Russian Academy of SciencesVladivostokRussia
  3. 3.Departamento de Bioquimica y Biologia MolecularUniversidad de SalamancaSpain

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