Archives of Virology

, Volume 153, Issue 5, pp 831–837 | Cite as

Chitosan as an adjuvant for parenterally administered inactivated influenza vaccines

Original Article

Abstract

The addition of 0.5% of a chitosan derivative to inactivated influenza vaccines injected parenterally resulted in a four or six to tenfold increase in antibody titres after a single-dose or two-dose intramuscular immunization of mice, respectively, in comparison with antibody titres after immunization without chitosan. Chitosan-adjuvanted vaccines enhanced antibody titers against drift variants of A- and B-type human influenza viruses four to six times compared with the vaccines without chitosan. Inactivated avian influenza virus A/H5N2 admixed with chitosan, when administered to mice challenged afterwards with the same virus, showed higher immunogenicity and protective efficacy compared with the antigen without chitosan.

Notes

Acknowledgments

The authors are deeply grateful to Dr. Smirnov, who kindly provided us with the mouse-adapted avian influenza virus A/H5N2 strain that was needed for our investigations.

References

  1. 1.
    Belshe RB, Gruber WC, Mendelman PM, Cho I, Reisinger K, Block SL, Wittes J, Iacusio D, Piedra P, Treanor J, King I, Kotloff K, Bernstein DI, Hayden FG, Zangwill K, Yan L, Wollf M (2000) Efficacy of vaccination with live attenuated, cold adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. J Pediatr 136:168–175PubMedCrossRefGoogle Scholar
  2. 2.
    Couch R (2000) Influenza: prospects for control. Ann Intern Med 133:992–998PubMedGoogle Scholar
  3. 3.
    De Jong J, Beyer W, Palache A, Rimmelzwaan G, Osterhaus A (2000) Mismatch between the 1997/1998 influenza vaccine and the major epidemic A/H3N2 virus strain as the cause of an inadequate vaccine-induce antibody response to this strain in the elderly. J Med Virol 61:94–99PubMedCrossRefGoogle Scholar
  4. 4.
    Felt O, Buri P, Curny R (1998) Chitosan, a unique polysaccharide for drug delivery. Drug Dev Ind Pharm 24:979–993PubMedGoogle Scholar
  5. 5.
    Gluck U, Gebbers J, Gluck R (1999) Phase 1 evaluation intranasal virosomal influenza vaccine with and without E. coli heat-labile toxin in adult volunteers. J Virol 73:7780–7786PubMedGoogle Scholar
  6. 6.
    Gross P, Hermogenes A, Sacks H, Lau J, Lewandowski R (1995) The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med 123:518–527PubMedGoogle Scholar
  7. 7.
    Hehme N, Engelman H, Kuenzel W, Neumeier E, Saenger R (2004) Immunogenicity of a monovalent aluminium-adjuvanted influenza whole virus vaccine for pandemic use. Virus Res 103:163–171PubMedCrossRefGoogle Scholar
  8. 8.
    Hirano S (1996) Chitin biotechnology application. Biotechnol Ann Rev 2:237–258CrossRefGoogle Scholar
  9. 9.
    Illum L, Jabbal-Gill I, Hincheliffe A, Fisher A, Davis S (2001) Chitosan as a novel nasal delivery system for vaccines. Drug Deliv 51:81–96CrossRefGoogle Scholar
  10. 10.
    Kendal A, Pereira M, Skehel J (1982) Concepts and procedures for laboratory-based influenza surveillance. WHO, GenevaGoogle Scholar
  11. 11.
    Mendelman PM, Rappaport R, Cho I, Block S, Gruber W, August M, Dawson D, Cordova J, Kemble G, Mahmood K, Palladino G, Lee MS, Razmpour A, Stoddard J, Forrest BF (2004) Live attenuated influenza vaccine induces cross-reactive antibody responses in children against an a/Fujian/411/2002-like H3N2 antigenic variant strain. Pediatr Infect Dis 23:1053–1055CrossRefGoogle Scholar
  12. 12.
    Mutsch M, Zhou W, Rhodes P, Bopp M, Chen RT, Linder T, Spyr C, Steffen R (2004) Use of the inactivated intranasal influenza vaccine and the risk of Bell’s palsy in Switzerland. New Engl J Med 350:896–903PubMedCrossRefGoogle Scholar
  13. 13.
    Nicholson K, Tyrrel D, Harrison P, Plotter C, Jennings R, Clark A, Shild G, Wood J, Yetts R, Seagroat V, Huggins A, Anderson S (1979) Clinical studies of monovalent inactivated whole virus and subunit A/USSR/77 (H1N1) vaccine: serological responses and clinical reactions. J Biol Stand 7:123–136PubMedCrossRefGoogle Scholar
  14. 14.
    Palache A (1997) Influenza vaccines: a reappraisal of their use. Drugs 54:841–856PubMedCrossRefGoogle Scholar
  15. 15.
    Palache A (2006) International meetings on pandemic preparedness and control. Infl Bull ESWI 21:6–7Google Scholar
  16. 16.
    Podda A (2001) The adjuvanted influenza vaccine with novel adjuvants: experience with the MF 59-adjuvanted vaccine. Vaccine 19:2637–2680CrossRefGoogle Scholar
  17. 17.
    Podda A, Del Guidice G (2003) MF 59-adjuvanted vaccines: increased immunogenicity with an optimal safety profile. Expert Rev Vaccines 2:197–204PubMedCrossRefGoogle Scholar
  18. 18.
    Potter C (1982) Inactivated influenza vaccine. In: Bear A (ed) Basic and applied influenza research. CRC Press, Boca Raton, pp 116–158Google Scholar
  19. 19.
    Smirnov Y, Lipatov A, van Beek R, Gitelman A, Osterhaus A, Claas E (2000) Characterization of a adaptation of an avian influenza A (H5N2) virus to a mammalian host. Acta Virol 41:1–8Google Scholar
  20. 20.
    Wood J, Williams M (1998) History of inactivated influenza vaccines. In: Nicholson K, Webster R, Hay A (eds) Textbook of influenza. Blackwell, London, pp 317–323Google Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Y. Ghendon
    • 1
  • S. Markushin
    • 1
  • G. Krivtsov
    • 1
  • I. Akopova
    • 1
  1. 1.Mechnikov Research Institute for Vaccines and SeraMoscowRussia

Personalised recommendations