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New Strategies to Overcome the Drawbacks of Currently Available Flu Vaccines

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Pharmaceutical Biotechnology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 655))

Abstract

Vaccination represents the most efficient tool to control morbidity and mortality resulting from influenza infections in humans. The currently licensed influenza vaccines provide good protection levels in healthy adults, whereas lower protection is generally achieved in ageing individuals who are at a higher risk of developing severe clinical manifestations. Future improvements in influenza vaccines should address the needs of high risk groups including the elderly, small children and chronic patients. Recently, due to the increased incidence of avian influenza pandemic outbreaks, the prevention of a potential human influenza pandemic turned into another crucial issue in the influenza vaccination field. The development and validation of manufacturing processes for efficient and safe pandemic vaccines became one of the top priorities of health, regulatory and funding agencies all over the world. In the pandemic context, the development of novel vaccines administered via the mucosal route may play a significant role by reducing virus shedding from infected individuals. This chapter provides insights in the limitations of existing manufacturing processes, new approaches to overcome limitation in vaccine production, mechanisms of action of current vaccines and discuss potential strategies to improve the immunogenicity and efficacy of influenza vaccines.

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References

  1. Lamb RA, Krug RM. Orthomyxoviridae: The viruses and their replication. In: Fields BN, Knipe DM, Howly PM, eds. Fields Virology. Philadelphia: Lippincott-Raven Publishers, 1996:1353–1395.

    Google Scholar 

  2. The Universal Virus Database ICTVdB: http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/index.htm

    Google Scholar 

  3. Nicholson KG. Human Influenza. In: Nicholson KG, Webster RG, Hay AJ, eds. Textbook of Influenza. Oxford: Blackwell Science; 1998:219–264.

    Google Scholar 

  4. Nicholson KG, Wood JM, Zambon M. Influenza. Lancet 2003; (362):1733–44.

    Article  CAS  PubMed  Google Scholar 

  5. Weekly epidemiological record, 2005; Nr. 33 (80):277–288.

    Google Scholar 

  6. Influenza report 2006, edited by Kamps BS, Hoffman C and Preisser W, Flying Publisher, 2006.

    Google Scholar 

  7. Hemmes JH, Winkler KC, Kool SM. Virus survival as a seasonal factor in influenza and polimyelitis. Nature 1960; (188):430–1.

    Article  CAS  PubMed  Google Scholar 

  8. 8 Smith W, Andrewes CH, Laidlaw PP. A virus obtained from influenza patients. Lancet 1933; (1):66–68.

    Article  Google Scholar 

  9. Wood JM, Williams MS. History of inactivated influenza vaccines. In: Nicholson KG, Webster RG, Hay AJ eds. Textbook of Influenza. Oxford: Blackwell Science: 1998:317–23.

    Google Scholar 

  10. Furminger IGS. Vaccine production. In: Nicholson KG, Webster RG, Hay AJ, eds. Textbook of Influenza Oxford: Blackwell Science Ltd: 1998:324–332.

    Google Scholar 

  11. Medema J, Wijnands DT, Palache AM. The role of MDCK-based influenza vaccine Influvac TC in inter(pandemics). International Congress Series 2004; 1263:822–825.

    Article  Google Scholar 

  12. Ozaki H, Govorkova EA, Li C et al. Generation of high-yielding influenza A viruses in African green monkey kidney (Vero) cells by reverse genetics. J Virol 2004; 78(4):1851–7.

    Article  CAS  PubMed  Google Scholar 

  13. Pau MG, Ophorst C, Koldijk MH et al. The human cell line PER.C6 provides a new manufacturing system for the production of influenza vaccines. Vaccine 2001; 19(17–19):2716–21.

    Article  CAS  PubMed  Google Scholar 

  14. Wang D, Christopher ME, Nagata LP et al. Intranasal immunization with liposome-encapsulated plasmid DNA encoding influenza virus hemagglutinin elicits mucosal, cellular and humoral immune responses. J Clin Virol 2004; 31(Suppl 1):S99–106.

    Article  CAS  Google Scholar 

  15. Tamura S, Tanimoto T, Kurata T. Mechanisms of broad cross-protection provided by influenza virus infection and their application to vaccines. Jpn J Infect Dis 2005; 58(4):195–207.

    CAS  PubMed  Google Scholar 

  16. Brett IC, Johansson BE. Immunization against influenza A virus: comparison of conventional inactivated, live-attenuated and recombinant baculovirus produced purified hemagglutinin and neuraminidase vaccines in a murine model system. Virology 2005; 339(2):273–80.

    Article  CAS  PubMed  Google Scholar 

  17. Van Kampen KR, Shi Z, Gao P et al. Safety and immunogenicity of adenovirus-vectored nasal and epicutaneous influenza vaccines in humans. Vaccine 2005; 23(8):1029–36.

    Article  PubMed  Google Scholar 

  18. Cassetti MC, Katz JM, Wood J. Report of a consultation on role of immunological assays to evaluate efficacy of influenza vaccines. Initiative for Vaccine Research and Global Influenza Programme, World Health Organization, Geneva, Switzerland, 2005. Vaccine 2006; 24(5):541–3.

    Article  PubMed  Google Scholar 

  19. Nichol KL. Efficacy/clinical effectiveness of inactivated influenza virus vaccines in adults. In: Nicholson KG, Webster RG, Hay AJ, eds. Textbook of Influenza. Oxford: Blackwell Science Ltd: 1998:358–372.

    Google Scholar 

  20. McElhaney JE, Xie D, Hager WD et al. T-cell responses are better correlates of vaccine protection in the elderly. J Immunol. 2006; 176(10):6333–9.

    CAS  PubMed  Google Scholar 

  21. Belshe RB, Couch RB, Glezen WP et al. Live attenuated intranasal influenza vaccine. Vaccine 2002; 20(29–30):3429–30.

    Article  PubMed  Google Scholar 

  22. Thomas PG, Keating R, Hulse-Post DJ et al. Cell-mediated protection in influenza infection. Emerg Infect Dis 2006; 12(1):48–54.

    CAS  PubMed  Google Scholar 

  23. Bresson JL, Perronne C, Launay O et al. Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial. Lancet 2006; 367(9523):1657–64.

    Article  CAS  PubMed  Google Scholar 

  24. Gupta RK, Relyved ER, Lindblad EB et al. Adjuvants—a balance between toxicity and adjuvanticity. Vaccine 1993; 11(3):293–306.

    Article  CAS  PubMed  Google Scholar 

  25. Glück R, Mischler R, Finkel Bf et al. Immunogenicity of new virosome influenza vaccine in the elderly people. Lancet 1994; (344):160–163.

    Article  PubMed  Google Scholar 

  26. Stephenson I, Bugarini R, Nicholson KG et al. Cross-reactivity to highly pathogenic avian influenza H5N1 viruses after vaccination with nonadjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a potential priming strategy. J Infect Dis 2005; 191(8):1210–5.

    Article  PubMed  Google Scholar 

  27. Banzhoff A, Nacci P, Podda A. A new MF59-adjuvanted influenza vaccine enhances the immune response in the elderly with chronic diseases: results from an immunogenicity meta-analysis. Gerontology 2003; 49(3):177–84.

    Article  CAS  PubMed  Google Scholar 

  28. Moser C, Metcalfe IC, Viret JF. Virosomal adjuvanted antigen delivery systems. Expert Rev Vaccines 2003; 2(2):189–96. Review. Erratum in: Expert Rev Vaccines 2003; 2(6):842.

    Article  CAS  PubMed  Google Scholar 

  29. Takeshita F, Tanaka T, Matsuda T et al. Toll-Like Receptor Adaptor Molecules Enhances Enhance DNA-Raised Adaptive Immune Responses against Influenza and Tumors through Activation of Innate Immunity. J Virol 2006; 80(13):6218–24.

    Article  CAS  PubMed  Google Scholar 

  30. Guillot L, Le Goffic R, Bloch S et al. Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem 2005; 280(7):5571–80.

    Article  CAS  PubMed  Google Scholar 

  31. Lund JM, Alexopoulou L, Sato A et al. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci USA 2004; 101(15):5598–5603.

    Article  CAS  PubMed  Google Scholar 

  32. Treanor J, Nolan C, O’Brien D et al. Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects. Vaccine 2006; 24(3):254–62.

    Article  CAS  PubMed  Google Scholar 

  33. Stephenson I, Zambon MC, Rudin A et al. Phase I evaluation of intranasal trivalent inactivated influenza vaccine with nontoxigenic Escherichia coli enterotoxin and novel biovector as mucosal adjuvants, using adult volunteers. J Virol 2006; 80(10):4962–70.

    Article  CAS  PubMed  Google Scholar 

  34. Eriksson AM, Schon KM, Lycke NY. The cholera toxin-derived CTA1-DD vaccine adjuvant administered intranasally does not cause inflammation or accumulate in the nervous tissues. J Immunol 2004; 173(5):3310–9.

    CAS  PubMed  Google Scholar 

  35. Helgeby A, Robson NC, Donachie AM et al. The combined CTA1-DD/ISCOM adjuvant vector promotes priming of mucosal and systemic immunity to incorporated antigens by specific targeting of B-cells. J Immunol 2006; 176(6):3697–706.

    CAS  PubMed  Google Scholar 

  36. Rimmelzwaan GF, Boon AC, Geelhoed-Mieras MM et al. Human airway epithelial cells present antigen to influenza virus-specific CD8+ CTL inefficiently after incubation with viral protein together with ISCOMATRIX. Vaccine 2004; 22(21–22):2769–75.

    Article  CAS  PubMed  Google Scholar 

  37. Coulter A, Harris R, Davis R et al. Intranasal vaccination with ISCOMATRIX adjuvanted influenza vaccine. Vaccine 2003; 21(9–10):946–9.

    Article  CAS  PubMed  Google Scholar 

  38. Ennis FA, Cruz J, Jameson J et al. Augmentation of human influenza A virus-specific cytotoxic T-lymphocyte memory by influenza vaccine and adjuvanted carriers (ISCOMS). Virology 1999; 259(2):256–61.

    Article  CAS  PubMed  Google Scholar 

  39. Borsutzky S, Kretschmer K, Becker PD et al. The mucosal adjuvant macrophage-activating lipopeptide-2 directly stimulates B-lymphocytes via the TLR2 without the need of accessory cells. J Immunol 2005; 174(10):6308–13.

    CAS  PubMed  Google Scholar 

  40. Muszkat M, Greenbaum E, Ben-Yehuda A et al. Local and systemic immune response in nursinghome elderly following intranasal or intramuscular immunization with inactivated influenza vaccine. Vaccine 2003; (21):1180–1186.

    Article  CAS  PubMed  Google Scholar 

  41. Glück U, Gebbers J-O, Glück R. Phase 1 evaluation of intranasal virosomal influenza vaccine with and without Escherichia coli heat-labile toxin in adult volunteers. J Virol 1999; 73(9):7780–7786.

    PubMed  Google Scholar 

  42. Epstein SL. Control of influenza virus infection by immunity to conserved viral features. Expert Rev Anti Infect Ther 2003; 1(4):627–38.

    Article  PubMed  Google Scholar 

  43. Deroo T, Jou WM, Fiers W. Recombinant neuraminidase vaccine protects against lethal influenza. Vaccine 1996; 14(6):561–9.

    Article  CAS  PubMed  Google Scholar 

  44. Epstein SL, Misplon JA, Lawson CM et al. Beta 2-microglobulin-deficient mice can be protected against influenza A infection by vaccination with vaccinia-influenza recombinants expressing hemagglutinin and neuraminidase. J Immunol 1993; 150(12):5484–93.

    CAS  PubMed  Google Scholar 

  45. Gianfrani C, Oseroff C, Sidney J et al. Human memory CTL response specific for influenza A virus is broad and multispecific. Hum Immunol 2000; 61(5):438–52.

    Article  CAS  PubMed  Google Scholar 

  46. Cox MM. Cell-based protein vaccines for influenza. Curr Opin Mol Ther 2005; 7(1):24–9.

    CAS  PubMed  Google Scholar 

  47. Thomas PG, Keating R, Hulse-Post DJ et al. Cell-mediated protection in influenza infection. Emerg Infect Dis 2006; 12(1):48–54.

    CAS  PubMed  Google Scholar 

  48. Turner SJ, Kedzierska K, Komodromou H et al. Lack of prominent peptide-major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T-cell populations. Nat Immunol 2005; 6(4):382–9.

    Article  CAS  PubMed  Google Scholar 

  49. Kedzierska K, Turner SJ, Doherty PC. Conserved T-cell receptor usage in primary and recall responses to an immunodominant influenza virus nucleoprotein epitope. Proc Natl Acad Sci USA 2004; 101(14):4942–7.

    Article  CAS  PubMed  Google Scholar 

  50. Fan J, Liang X, Horton MS et al. Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets and rhesus monkeys. Vaccine 2004; 22(23–24):2993–3003.

    Article  CAS  PubMed  Google Scholar 

  51. Jegerlehner A, Schmitz N, Storni T et al. Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. J Immunol 2004; 172(9):5598–605.

    CAS  PubMed  Google Scholar 

  52. Ozaki T, Yauchi M, Xin KQ et al. Cross-reactive protection against influenza A virus by a topically applied DNA vaccine encoding M gene with adjuvant. Viral Immunol 2005; 18(2):373–80.

    Article  CAS  PubMed  Google Scholar 

  53. Falcon AM, Fernandez-Sesma A, Nakaya Y et al. Attenuation and immunogenicity in mice of temperature-sensitive influenza viruses expressing truncated NS1 proteins. J Gen Virol 2005; 86(Pt 10):2817–21.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Etna Biotech S.r.l., Piazza Stesicoro 59, 95131, Catania, Italy

    Epifanio Fichera & Reinhard Glueck

  2. Berna Biotech Ltd. a Crucell NV, Berne, Switzerland

    Diana Felnerova & Jean-François Viret

  3. Mibiotec Limited, Worblaufen, Switzerland

    Robert Mischler

Authors
  1. Epifanio Fichera
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  2. Diana Felnerova
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  3. Robert Mischler
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  4. Jean-François Viret
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  5. Reinhard Glueck
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Corresponding author

Correspondence to Epifanio Fichera .

Editor information

Editors and Affiliations

  1. Department of Vaccinology and Applied Microbiology, HZI-Helmholtz Centre for Infection Research, Braunschweig, Germany

    Carlos A. Guzmán MD, PhD

  2. Wyeth Research, Collegeville, Pennsylvania, USA

    Giora Z. Feuerstein MD, MSc, FAHA

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© 2009 Landes Bioscience and Springer Science+Business Media

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Fichera, E., Felnerova, D., Mischler, R., Viret, JF., Glueck, R. (2009). New Strategies to Overcome the Drawbacks of Currently Available Flu Vaccines. In: Guzmán, C.A., Feuerstein, G.Z. (eds) Pharmaceutical Biotechnology. Advances in Experimental Medicine and Biology, vol 655. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1132-2_15

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