Skip to main content
SpringerLink
Log in

Influenza Virosomes as Antigen Delivery System

  • Chapter
  • First Online:
Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines

Abstract

Over 15 years of clinical experience with vaccines based on Influenza virosomes has generated a considerable track record, featuring an excellent safety and tolerability profile as well as convincing immunogenicity and efficacy data. In the past decade, a second generation of Influenza virosomes has been developed and validated as a versatile, standalone carrier, and adjuvant system for heterologous subunit antigens.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Jennings GT, Bachmann MF (2008) The coming of age of virus-like particle vaccines. Biol Chem 389(5):521–536

    Article  PubMed  CAS  Google Scholar 

  2. Jansen KU, Conner ME, Estes MK (2010) Virus-like particles as vaccines and vaccine delivery systems. In: Levine MM, Dougan G, Good MF, Liu MA, Nabel GJ, Nataro JP et al (eds) New generation vaccines, 4th edn. Informa Healthcare, New York, pp 298–305

    Google Scholar 

  3. Haynes JR (2009) Influenza virus-like particle vaccines. Expert Rev Vaccines 8(4):435–445

    Article  PubMed  CAS  Google Scholar 

  4. Cox MM (2008) Progress on baculovirus-derived influenza vaccines. Curr Opin Mol Ther 10(1):56–61

    PubMed  CAS  Google Scholar 

  5. Datta SA, Rein A (2009) Preparation of recombinant HIV-1 gag protein and assembly of virus-like particles in vitro. Methods Mol Biol 485:197–208

    Article  PubMed  CAS  Google Scholar 

  6. Almeida JD, Edwards DC, Brand CM, Heath TD (1975) Formation of virosomes from influenza subunits and liposomes. Lancet 2(7941):899–901

    Article  PubMed  CAS  Google Scholar 

  7. Morein B, Helenius A, Simons K, Pettersson R, Kaariainen L, Schirrmacher V (1978) Effective subunit vaccines against an enveloped animal virus. Nature 276(5689):715–718

    Article  PubMed  CAS  Google Scholar 

  8. Zurbriggen R, Moser C, Rasi S, Kammer AR, Amacker M, Westerfeld N (inventors) (2008) Pevion Biotech, assignee. Virosomes comprising hemagglutinin derived from an influenza virus produced in a cell line, compositions, methods of manufacturing, use thereof. WO 2009/000433 A1

    Google Scholar 

  9. Stegmann T, Morselt HW, Booy FP, van Breemen JF, Scherphof G, Wilschut J (1987) Functional reconstitution of influenza virus envelopes. EMBO J 6(9):2651–2659

    PubMed  CAS  Google Scholar 

  10. Gluck R, Mischler R, Brantschen S, Just M, Althaus B, Cryz SJ Jr (1992) Immunopotentiating reconstituted influenza virus virosome vaccine delivery system for immunization against hepatitis A. J Clin Invest 90(6):2491–2495

    Article  PubMed  CAS  Google Scholar 

  11. Gluck R (1999) Adjuvant activity of immunopotentiating reconstituted influenza virosomes (IRIVs). Vaccine 17(13–14):1782–1787

    Article  PubMed  CAS  Google Scholar 

  12. Bovier PA (2008) Epaxal: a virosomal vaccine to prevent hepatitis A infection. Expert Rev Vaccines 7(8):1141–1150

    Article  PubMed  CAS  Google Scholar 

  13. Gluck R, Walti E (2000) Biophysical validation of Epaxal Berna, a hepatitis A vaccine adjuvanted with immunopotentiating reconstituted influenza virosomes (IRIV). Dev Biol (Basel) 103:189–197

    CAS  Google Scholar 

  14. Zurbriggen R, Novak-Hofer I, Seelig A, Gluck R (2000) IRIV-adjuvanted hepatitis A vaccine: in vivo absorption and biophysical characterization. Prog Lipid Res 39(1):3–18

    Article  PubMed  CAS  Google Scholar 

  15. Herzog C, Hartmann K, Kunzi V et al (2009) Eleven years of Inflexal V-a virosomal adjuvanted influenza vaccine. Vaccine 27(33):4381–4387

    Article  PubMed  CAS  Google Scholar 

  16. Wilschut J (2009) Influenza vaccines: the virosome concept. Immunol Lett 122(2):118–121

    Article  PubMed  CAS  Google Scholar 

  17. Mischler R, Metcalfe IC (2002) Inflexal V a trivalent virosome subunit influenza vaccine: production. Vaccine 20(Suppl 5):B17–B23

    Article  PubMed  CAS  Google Scholar 

  18. de Bruijn IA, Nauta J, Gerez L, Palache AM (2006) The virosomal influenza vaccine Invivac: immunogenicity and tolerability compared to an adjuvanted influenza vaccine (Fluad) in elderly subjects. Vaccine 24(44–46):6629–6631

    Article  PubMed  Google Scholar 

  19. Gluck R (2002) Intranasal immunization against influenza. J Aerosol Med 15(2):221–228

    Article  PubMed  Google Scholar 

  20. Mutsch M, Zhou W, Rhodes P et al (2004) Use of the inactivated intranasal influenza vaccine and the risk of Bell’s palsy in Switzerland. N Engl J Med 350(9):896–903

    Article  PubMed  CAS  Google Scholar 

  21. Zurbriggen R, Metcalfe IC, Gluck R, Viret JF, Moser C (2003) Nonclinical safety evaluation of Escherichia coli heat-labile toxin mucosal adjuvant as a component of a nasal influenza vaccine. Expert Rev Vaccines 2(2):295–304

    Article  PubMed  CAS  Google Scholar 

  22. Zurbriggen R (2003) Immunostimulating reconstituted influenza virosomes. Vaccine 21(9–10):921–924

    Article  PubMed  CAS  Google Scholar 

  23. Holzer BR, Hatz C, Schmidt-Sissolak D, Gluck R, Althaus B, Egger M (1996) Immunogenicity and adverse effects of inactivated virosome versus alum-adsorbed hepatitis A vaccine: a randomized controlled trial. Vaccine 14(10):982–986

    Article  PubMed  CAS  Google Scholar 

  24. Clarke PD, Adams P, Ibanez R, Herzog C (2006) Rate, intensity, and duration of local reactions to a virosome-adjuvanted vs. an aluminium-adsorbed hepatitis A vaccine in UK travellers. Travel Med Infect Dis 4(6):313–318

    Article  PubMed  Google Scholar 

  25. Huckriede A, Bungener L, Stegmann T et al (2005) The virosome concept for influenza vaccines. Vaccine 23(Suppl 1):S26–S38

    Article  PubMed  Google Scholar 

  26. Calcagnile S, Zuccotti GV (2010) The virosomal adjuvanted influenza vaccine. Expert Opin Biol Ther 10(2):191–200

    Article  PubMed  Google Scholar 

  27. Kursteiner O, Moser C, Lazar H, Durrer P (2006) Inflexal V—the influenza vaccine with the lowest ovalbumin content. Vaccine 24(44–46):6632–6635

    Article  PubMed  CAS  Google Scholar 

  28. Thompson FM, Porter DW, Okitsu SL et al (2008) Evidence of blood stage efficacy with a virosomal malaria vaccine in a phase IIa clinical trial. PLoS One 3(1):e1493

    Article  PubMed  Google Scholar 

  29. Wiedermann U, Wiltschke C, Jasinska J et al (2010) A virosomal formulated Her-2/neu multi-peptide vaccine induces Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I study. Breast Cancer Res Treat 119(3):673–683

    Article  PubMed  CAS  Google Scholar 

  30. Bomsel M, Tudor D, Drillet AS et al (2011) Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges. Immunity 34(2):269–280

    Article  PubMed  CAS  Google Scholar 

  31. Okitsu SL, Silvie O, Westerfeld N et al (2007) A virosomal malaria peptide vaccine elicits a long-lasting sporozoite-inhibitory antibody response in a phase 1a clinical trial. PLoS One 2(12):e1278

    Article  PubMed  Google Scholar 

  32. Zurbriggen R, Amacker M, Kammer AR et al (2005) Virosome-based active immunization targets soluble amyloid species rather than plaques in a transgenic mouse model of Alzheimer’s disease. J Mol Neurosci 27(2):157–166

    Article  PubMed  CAS  Google Scholar 

  33. Liu X, Siegrist S, Amacker M, Zurbriggen R, Pluschke G, Seeberger PH (2006) Enhancement of the immunogenicity of synthetic carbohydrates by conjugation to virosomes: a leishmaniasis vaccine candidate. ACS Chem Biol 1(3):161–164

    Article  PubMed  CAS  Google Scholar 

  34. Nallet S, Amacker M, Westerfeld N et al (2009) Respiratory syncytial virus subunit vaccine based on a recombinant fusion protein expressed transiently in mammalian cells. Vaccine 27(46):6415–6419

    Article  PubMed  CAS  Google Scholar 

  35. Moser C, Amacker M, Zurbriggen R (2011) Influenza virosomes as a vaccine adjuvant and carrier system. Expert Rev Vaccines 10(4):437–446. Accessed

    Article  PubMed  CAS  Google Scholar 

  36. Pevion Biotech AG Homepage (2011). www.pevion.com

  37. Cech PG, Aebi T, Abdallah MS et al (2011) Virosome-formulated Plasmodium falciparum AMA-1 & CSP derived peptides as malaria vaccine: randomized phase 1b trial in semi-immune adults & children. PLoS One 6(7):e22273

    Article  PubMed  CAS  Google Scholar 

  38. Kammer AR, Amacker M, Rasi S et al (2007) A new and versatile virosomal antigen delivery system to induce cellular and humoral immune responses. Vaccine 25(41):7065–7074

    Article  PubMed  CAS  Google Scholar 

  39. Bungener L, Serre K, Bijl L et al (2002) Virosome-mediated delivery of protein antigens to dendritic cells. Vaccine 20(17–18):2287–2295

    Article  PubMed  CAS  Google Scholar 

  40. Bungener L, Huckriede A, de Mare A, de Vries-Idema J, Wilschut J, Daemen T (2005) Virosome-mediated delivery of protein antigens in vivo: efficient induction of class I MHC-restricted cytotoxic T lymphocyte activity. Vaccine 23(10):1232–1241

    Article  PubMed  CAS  Google Scholar 

  41. Amacker M, Engler O, Kammer AR et al (2005) Peptide-loaded chimeric influenza virosomes for efficient in vivo induction of cytotoxic T cells. Int Immunol 17(6):695–704 Accessed 26 Aug 2011

    Article  PubMed  CAS  Google Scholar 

  42. Waelti ER, Gluck R (1998) Delivery to cancer cells of antisense L-myc oligonucleotides incorporated in fusogenic, cationic-lipid-reconstituted influenza-virus envelopes (cationic virosomes). Int J Cancer 77(5):728–733

    Article  PubMed  CAS  Google Scholar 

  43. Schoen P, Chonn A, Cullis PR, Wilschut J, Scherrer P (1999) Gene transfer mediated by fusion protein hemagglutinin reconstituted in cationic lipid vesicles. Gene Ther 6(5):823–832

    Article  PubMed  CAS  Google Scholar 

  44. Cusi MG, Terrosi C, Savellini GG, Di Genova G, Zurbriggen R, Correale P (2004) Efficient delivery of DNA to dendritic cells mediated by influenza virosomes. Vaccine 22(5–6):735–739

    PubMed  Google Scholar 

  45. de Jonge J, Holtrop M, Wilschut J, Huckriede A (2006) Reconstituted influenza virus envelopes as an efficient carrier system for cellular delivery of small-interfering RNAs. Gene Ther 13(5):400–411

    Article  PubMed  Google Scholar 

  46. de Jonge J, Leenhouts JM, Holtrop M et al (2007) Cellular gene transfer mediated by influenza virosomes with encapsulated plasmid DNA. Biochem J 405(1):41–49

    PubMed  Google Scholar 

  47. Waelti E, Wegmann N, Schwaninger R et al (2002) Targeting her-2/neu with antirat Neu virosomes for cancer therapy. Cancer Res 62(2):437–444

    PubMed  CAS  Google Scholar 

  48. de Jonge J, Amorij JP, Hinrichs WL, Wilschut J, Huckriede A, Frijlink HW (2007) Inulin sugar glasses preserve the structural integrity and biological activity of influenza virosomes during freeze-drying and storage. Eur J Pharm Sci 32(1):33–44

    Article  PubMed  Google Scholar 

  49. Schumacher R, Adamina M, Zurbriggen R et al (2004) Influenza virosomes enhance class I restricted CTL induction Through CD4+ T cell activation. Vaccine 22:714–723

    Article  PubMed  CAS  Google Scholar 

  50. Daemen T, de Mare A, Bungener L, de Jonge J, Huckriede A, Wilschut J (2005) Virosomes for antigen and DNA delivery. Adv Drug Deliv Rev 57(3):451–463

    Article  PubMed  CAS  Google Scholar 

  51. Angel J, Chaperot L, Molens JP et al (2007) Virosome-mediated delivery of tumor antigen to plasmacytoid dendritic cells. Vaccine 25(19):3913–3921

    Article  PubMed  CAS  Google Scholar 

  52. Hofer U, Lehmann AD, Waelti E, Amacker M, Gehr P, Rothen-Rutishauser B (2009) Virosomes can enter cells by non-phagocytic mechanisms. J Liposome Res 19(4):301–309

    Article  PubMed  CAS  Google Scholar 

  53. Genton B, Pluschke G, Degen L et al (2007) A randomized placebo-controlled phase Ia malaria vaccine trial of two virosome-formulated synthetic peptides in healthy adult volunteers. PLoS One 2(10):e1018

    Article  PubMed  Google Scholar 

  54. Mymetics Corp Homepage (2011). www.mymetics.com

  55. Bachmann MF, Jennings GT (2010) Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 10(11):787–796

    Article  PubMed  CAS  Google Scholar 

  56. Ishii KJ, Akira S (2007) Toll or toll-free adjuvant path toward the optimal vaccine development. J Clin Immunol 27(4):363–371

    Article  PubMed  CAS  Google Scholar 

  57. De Gregorio E, D’Oro U, Wack A (2009) Immunology of TLR-independent vaccine adjuvants. Curr Opin Immunol 21(3):339–345

    Article  PubMed  Google Scholar 

  58. Kool M, Petrilli V, De ST et al (2008) Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J Immunol 181(6):3755–3759

    PubMed  CAS  Google Scholar 

  59. Tritto E, Mosca F, De GE (2009) Mechanism of action of licensed vaccine adjuvants. Vaccine 27(25–26):3331–3334

    Article  PubMed  CAS  Google Scholar 

  60. Harandi AM, Davies G, Olesen OF (2009) Vaccine adjuvants: scientific challenges and strategic initiatives. Expert Rev Vaccines 8(3):293–298

    Article  PubMed  CAS  Google Scholar 

  61. Petrovsky N (2008) Freeing vaccine adjuvants from dangerous immunological dogma. Expert Rev Vaccines 7(1):7–10

    Article  PubMed  CAS  Google Scholar 

  62. Mastelic B, Ahmed S, Egan WM et al (2010) Mode of action of adjuvants: implications for vaccine safety and design. Biologicals 38(5):594–601

    Article  PubMed  CAS  Google Scholar 

  63. The European Medicines Agency (2005) Evaluation of Medicines for Human Use, Committee for medicinal products for human use (CHMP), Guideline on adjuvants in vaccines for human use. EMEA/CHMP/VEG/134716/2004.

    Google Scholar 

  64. Sesardic D (2006) Regulatory considerations on new adjuvants and delivery systems. Vaccine 24(Suppl 2):S2–S7

    PubMed  Google Scholar 

  65. Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann MF (2008) Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol 38(5):1404–1413

    Article  PubMed  CAS  Google Scholar 

  66. Amacker M, Moese S, Kammer AR, Helenius A, Zurbriggen R (2009) Influenza virosomes as delivery systems for antigens. In: Jorgensen L, Nielsen HM (eds) Delivery technologies for biopharmaceuticals: peptides, proteins, nucleic acids, and vaccines, 1st edn. Wiley, Chichester, West Sussex, UK, pp 377–393

    Google Scholar 

  67. Junt T, Moseman EA, Iannacone M et al (2007) Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature 450(7166):110–114

    Article  PubMed  CAS  Google Scholar 

  68. Carrasco YR, Batista FD (2007) B cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node. Immunity 27(1):160–171

    Article  PubMed  CAS  Google Scholar 

  69. Bachmann MF, Speiser DE, Ohashi PS (1997) Functional management of an antiviral cytotoxic T-cell response. J Virol 71(8):5764–5768

    PubMed  CAS  Google Scholar 

  70. Justewicz DM, Doherty PC, Webster RG (1995) The B-cell response in lymphoid tissue of mice immunized with various antigenic forms of the influenza virus hemagglutinin. J Virol 69(9):5414–5421

    PubMed  CAS  Google Scholar 

  71. Liu WC, Lin SC, Yu YL, Chu CL, Wu SC (2010) Dendritic cell activation by recombinant hemagglutinin proteins of H1N1 and H5N1 influenza A viruses. J Virol 84(22):12011–12017

    Article  PubMed  CAS  Google Scholar 

  72. Song H, Wittman V, Byers A et al (2010) In vitro stimulation of human influenza-specific CD8+ T cells by dendritic cells pulsed with an influenza virus-like particle (VLP) vaccine. Vaccine 28(34):5524–5532

    Article  PubMed  CAS  Google Scholar 

  73. Barton GM (2007) Viral recognition by Toll-like receptors. Semin Immunol 19(1):33–40

    Article  PubMed  CAS  Google Scholar 

  74. McCoy K, Tatsis N, Korioth-Schmitz B et al (2007) Effect of preexisting immunity to adenovirus human serotype 5 antigens on the immune responses of nonhuman primates to vaccine regimens based on human- or chimpanzee-derived adenovirus vectors. J Virol 81(12):6594–6604

    Article  PubMed  CAS  Google Scholar 

  75. Sharpe S, Polyanskaya N, Dennis M et al (2001) Induction of simian immunodeficiency virus (SIV)-specific CTL in rhesus macaques by vaccination with modified vaccinia virus Ankara expressing SIV transgenes: influence of pre-existing anti-vector immunity. J Gen Virol 82(Pt 9):2215–2223

    PubMed  CAS  Google Scholar 

  76. Jegerlehner A, Wiesel M, Dietmeier K et al (2010) Carrier induced epitopic suppression of antibody responses induced by virus-like particles is a dynamic phenomenon caused by carrier-specific antibodies. Vaccine 28(33):5503–5512

    Article  PubMed  CAS  Google Scholar 

  77. Brokstad KA, Cox RJ, Eriksson JC, Olofsson J, Jonsson R, Davidsson A (2001) High prevalence of influenza specific antibody secreting cells in nasal mucosa. Scand J Immunol 54(1–2):243–247

    Article  PubMed  CAS  Google Scholar 

  78. Peduzzi E, Westerfeld N, Zurbriggen R, Pluschke G, Daubenberger CA (2008) Contribution of influenza immunity and virosomal-formulated synthetic peptide to cellular immune responses in a phase I subunit malaria vaccine trial. Clin Immunol 127(2):188–197

    Article  PubMed  CAS  Google Scholar 

  79. Zurbriggen R, Gluck R (1999) Immunogenicity of IRIV- versus alum-adjuvanted diphtheria and tetanus toxoid vaccines in influenza primed mice. Vaccine 17(11–12):1301–1305

    Article  PubMed  CAS  Google Scholar 

  80. Wilschut J, de Jonge J, Huckriede A, Amorij JP, Hinrichs WL, Frijlink HW (2007) Preservation of influenza virosome structure and function during freeze-drying and storage. J Liposome Res 17(3–4):173–182

    Article  PubMed  CAS  Google Scholar 

  81. Van der Wielen M, Vertruyen A, Froesner G et al (2007) Immunogenicity and safety of a pediatric dose of a virosome-adjuvanted hepatitis A vaccine: a controlled trial in children aged 1–16 years. Pediatr Infect Dis J 26(8):705–710

    Article  Google Scholar 

  82. Lamb RA, Krug RM (2001) Orthomyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fields virology, 4th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1487–1531

    Google Scholar 

  83. Felnerova D, Viret JF, Gluck R, Moser C (2004) Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs. Curr Opin Biotechnol 15(6):518–529

    Article  PubMed  CAS  Google Scholar 

  84. Khoshnejad M, Young PR, Toth I, Minchin RF (2007) Modified influenza virosomes: recent advances and potential in gene delivery. Curr Med Chem 14(29):3152–3156

    Article  PubMed  CAS  Google Scholar 

  85. Moser C, Amacker M, Kammer AR, Rasi S, Westerfeld N, Zurbriggen R (2007) Influenza virosomes as a combined vaccine carrier and adjuvant system for prophylactic and therapeutic immunizations. Expert Rev Vaccines 6(5):711–721

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pevion Biotech AG, Worblentalstrasse 32, CH-3063, Ittigen, Switzerland

    Christian Moser & Mario Amacker

Authors
  1. Christian Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mario Amacker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christian Moser .

Editor information

Editors and Affiliations

  1. Novartis Vaccines Research, Cambridge, 02139, Massachusetts, USA

    Manmohan Singh

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Moser, C., Amacker, M. (2013). Influenza Virosomes as Antigen Delivery System. In: Singh, M. (eds) Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-5380-2_14

Download citation

Publish with us

Policies and ethics

Search

Navigation