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Virus-Like Particles as Efficient Delivery Platform to Induce a Potent Immune Response

  • Fabien Rebeaud
  • Martin BachmannEmail author
Chapter

Abstract

Virus-like particles (VLPs) are spontaneously formed structures upon self-assembly of viral capsid proteins. Similar to viruses, VLPs have a repetitive surface structure and an optimal size to induce potent immune responses. In contrast to viruses, VLPs are devoid of viral genetic material and are therefore replication-deficient and non-pathogenic. Their unique advantages in terms of safety and immunogenicity together with their high versatility make VLPs an attractive vaccine-technology. Using various strategies, virtually any kind of molecule can be presented to the immune system on the surface of VLPs. This offers a broad spectrum of applications, ranging from the development of classical prophylactic vaccines to therapeutic vaccines against non-communicable diseases and even vaccines for the treatment of smoking addiction. With the registration of VLP-based prophylactic vaccines against Hepatitis B virus and Human papilloma virus, this vaccination strategy has proven its viability in the vaccines market. This chapter focuses on the different strategies existing for developing VLP vaccines, gives an overview of the VLP vaccine candidates currently clinically tested, thereby highlighting the successes and risks linked to the development of these immunotherapies.

Keywords

Virus-like particles Vaccine delivery Infectious disease Humoral immunity Cellular immunity 

References

  1. Adams SE, Dawson KM, Gull K, Kingsman SM, Kingsman AJ (1987) The expression of hybrid HIV:Ty virus-like particles in yeast. Nature 329:68–70PubMedGoogle Scholar
  2. Ambuhl PM, Tissot AC, Fulurija A, Maurer P, Nussberger J, Sabat R, Nief V, Schellekens C, Sladko K, Roubicek K, Pfister T, Rettenbacher M, Volk HD, Wagner F, Muller P, Jennings GT, Bachmann MF (2007) A vaccine for hypertension based on virus-like particles: preclinical efficacy and phase I safety and immunogenicity. J Hypertens 25:63–72PubMedGoogle Scholar
  3. Bachmann MF, Dyer MR (2004) Therapeutic vaccination for chronic diseases: a new class of drugs in sight. Nat Rev Drug Discov 3:81–88PubMedGoogle Scholar
  4. Bachmann MF, Jennings GT (2010) Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 10:787–796PubMedGoogle Scholar
  5. Bachmann MF, Zinkernagel RM (1996) The influence of virus structure on antibody responses and virus serotype formation. Immunol Today 17:553–558PubMedGoogle Scholar
  6. Bachmann MF, Rohrer UH, Kundig TM, Burki K, Hengartner H, Zinkernagel RM (1993) The influence of antigen organization on B cell responsiveness. Science 262:1448–1451PubMedGoogle Scholar
  7. Bachmann MF, Kalinke U, Althage A, Freer G, Burkhart C, Roost H, Aguet M, Hengartner H, Zinkernagel RM (1997) The role of antibody concentration and avidity in antiviral protection. Science 276:2024–2027PubMedGoogle Scholar
  8. Bachmann MF, Beerli RR, Agnellini P, Wolint P, Schwarz K, Oxenius A (2006) Long-lived memory CD8+ T cells are programmed by prolonged antigen exposure and low levels of cellular activation. Eur J Immunol 36:842–854PubMedGoogle Scholar
  9. Ball JM, Graham DY, Opekun AR, Gilger MA, Guerrero RA, Estes MK (1999) Recombinant Norwalk virus-like particles given orally to volunteers: phase I study. Gastroenterology 117:40–48PubMedGoogle Scholar
  10. Bansal GP, Hatfield JA, Dunn FE, Kramer AA, Brady F, Riggin CH, Collett MS, Yoshimoto K, Kajigaya S, Young NS (1993) Candidate recombinant vaccine for human B19 parvovirus. J Infect Dis 167:1034–1044PubMedGoogle Scholar
  11. Baric RS, Yount B, Lindesmith L, Harrington PR, Greene SR, Tseng FC, Davis N, Johnston RE, Klapper DG, Moe CL (2002) Expression and self-assembly of Norwalk virus capsid protein from Venezuelan equine encephalitis virus replicons. J Virol 76:3023–3030PubMedGoogle Scholar
  12. Bayer ME, Blumberg BS, Werner B (1968) Particles associated with Australia antigen in the sera of patients with leukaemia, Down’s syndrome and hepatitis. Nature 218:1057–1059PubMedGoogle Scholar
  13. Belyaev AS, Roy P (1993) Development of baculovirus triple and quadruple expression vectors: co-expression of three or four bluetongue virus proteins and the synthesis of bluetongue virus-like particles in insect cells. Nucleic Acids Res 21:1219–1223PubMedGoogle Scholar
  14. Bernstein DI, Sahly HM, Keitel WA, Wolff M, Simone G, Segawa C, Wong S, Shelly D, Young NS, Dempsey W (2011) Safety and immunogenicity of a candidate parvovirus B19 vaccine. Vaccine 29:7357–7363PubMedGoogle Scholar
  15. Bessa J, Schmitz N, Hinton HJ, Schwarz K, Jegerlehner A, Bachmann MF (2008) Efficient induction of mucosal and systemic immune responses by virus-like particles administered intranasally: implications for vaccine design. Eur J Immunol 38:114–126PubMedGoogle Scholar
  16. Borisova G, Borschukova Wanst O, Mezule G, Skrastina D, Petrovskis I, Dislers A, Pumpens P, Grens E (1996) Spatial structure and insertion capacity of immunodominant region of hepatitis B core antigen. Intervirology 39:16–22PubMedGoogle Scholar
  17. Brody DL, Holtzman DM (2008) Active and passive immunotherapy for neurodegenerative disorders. Annu Rev Neurosci 31:175–193PubMedGoogle Scholar
  18. Buonaguro L, Tornesello ML, Buonaguro FM (2007) Human immunodeficiency virus type 1 subtype distribution in the worldwide epidemic: pathogenetic and therapeutic implications. J Virol 81:10209–10219PubMedGoogle Scholar
  19. Buonamassa DT, Greer CE, Capo S, Yen TS, Galeotti CL, Bensi G (2002) Yeast coexpression of human papillomavirus types 6 and 16 capsid proteins. Virology 293:335–344PubMedGoogle Scholar
  20. Caldeira Jdo C, Medford A, Kines RC, Lino CA, Schiller JT, Chackerian B, Peabody DS (2010) Immunogenic display of diverse peptides, including a broadly cross-type neutralizing human papillomavirus L2 epitope, on virus-like particles of the RNA bacteriophage PP7. Vaccine 28:4384–4393PubMedGoogle Scholar
  21. Cane PA (2001) Molecular epidemiology of respiratory syncytial virus. Rev Med Virol 11:103–116PubMedGoogle Scholar
  22. Chackerian B, Lowy DR, Schiller JT (1999) Induction of autoantibodies to mouse CCR5 with recombinant papillomavirus particles. Proc Natl Acad Sci USA 96:2373–2378PubMedGoogle Scholar
  23. Chackerian B, Lowy DR, Schiller JT (2001) Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies. J Clin Invest 108:415–423PubMedGoogle Scholar
  24. Chackerian B, Lenz P, Lowy DR, Schiller JT (2002) Determinants of autoantibody induction by conjugated papillomavirus virus-like particles. J Immunol 169:6120–6126PubMedGoogle Scholar
  25. Chackerian B, Briglio L, Albert PS, Lowy DR, Schiller JT (2004) Induction of autoantibodies to CCR5 in macaques and subsequent effects upon challenge with an R5-tropic simian/human immunodeficiency virus. J Virol 78:4037–4047PubMedGoogle Scholar
  26. Chackerian B, Rangel M, Hunter Z, Peabody DS (2006) Virus and virus-like particle-based immunogens for Alzheimer’s disease induce antibody responses against amyloid-beta without concomitant T cell responses. Vaccine 24:6321–6331PubMedGoogle Scholar
  27. Conway MJ, Cruz L, Alam S, Christensen ND, Meyers C (2011) Cross-neutralization potential of native human papillomavirus N-terminal L2 epitopes. PLoS One 6:e16405PubMedGoogle Scholar
  28. Cooper CL, Davis HL, Morris ML, Efler SM, Adhami MA, Krieg AM, Cameron DW, Heathcote J (2004) CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study. J Clin Immunol 24:693–701PubMedGoogle Scholar
  29. Cornuz J, Zwahlen S, Jungi WF, Osterwalder J, Klingler K, van Melle G, Bangala Y, Guessous I, Muller P, Willers J, Maurer P, Bachmann MF, Cerny T (2008) A vaccine against nicotine for smoking cessation: a randomized controlled trial. PLoS One 3:e2547PubMedGoogle Scholar
  30. Crompton PD, Pierce SK, Miller LH (2010) Advances and challenges in malaria vaccine development. J Clin Invest 120:4168–4178PubMedGoogle Scholar
  31. De Filette M, Ramne A, Birkett A, Lycke N, Lowenadler B, Min Jou W, Saelens X, Fiers W (2006) The universal influenza vaccine M2e-HBc administered intranasally in combination with the adjuvant CTA1-DD provides complete protection. Vaccine 24:544–551PubMedGoogle Scholar
  32. Denis J, Acosta-Ramirez E, Zhao Y, Hamelin ME, Koukavica I, Baz M, Abed Y, Savard C, Pare C, Lopez Macias C, Boivin G, Leclerc D (2008) Development of a universal influenza A vaccine based on the M2e peptide fused to the papaya mosaic virus (PapMV) vaccine platform. Vaccine 26(27–28):3395–3403PubMedGoogle Scholar
  33. Dudas RA, Karron RA (1998) Respiratory syncytial virus vaccines. Clin Microbiol Rev 11:430–439PubMedGoogle Scholar
  34. El-Kamary SS, Pasetti MF, Mendelman PM, Frey SE, Bernstein DI, Treanor JJ, Ferreira J, Chen WH, Sublett R, Richardson C, Bargatze RF, Sztein MB, Tacket CO (2010) Adjuvanted intranasal Norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues. J Infect Dis 202:1649–1658PubMedGoogle Scholar
  35. Emeny RT, Wheeler CM, Jansen KU, Hunt WC, Fu TM, Smith JF, MacMullen S, Esser MT, Paliard X (2002) Priming of human papillomavirus type 11-specific humoral and cellular immune responses in college-aged women with a virus-like particle vaccine. J Virol 76:7832–7842PubMedGoogle Scholar
  36. Fang NX, Frazer IH, Fernando GJ (2000) Differences in the post-translational modifications of human papillomavirus type 6b major capsid protein expressed from a baculovirus system compared with a vaccinia virus system. Biotechnol Appl Biochem 32:27–33PubMedGoogle Scholar
  37. Fiers W, De Filette M, El Bakkouri K, Schepens B, Roose K, Schotsaert M, Birkett A, Saelens X (2009) M2e-Based universal influenza A vaccine. Vaccine 27:6280–6283PubMedGoogle Scholar
  38. Garcia JA (2011) Sipuleucel-T in patients with metastatic castration-resistant prostate cancer: an insight for oncologists. Ther Adv Med Oncol 3:101–108PubMedGoogle Scholar
  39. Gatto D, Martin SW, Bessa J, Pellicioli E, Saudan P, Hinton HJ, Bachmann MF (2007) Regulation of memory antibody levels: the role of persisting antigen versus plasma cell life span. J Immunol 178:67–76PubMedGoogle Scholar
  40. Gilmour JE, Senior JM, Burns NR, Esnouf MP, Gull K, Kingsman SM, Kingsman AJ, Adams SE (1989) A novel method for the purification of HIV-1 p24 protein from hybrid Ty virus-like particles (Ty-VLPs). AIDS 3:717–723PubMedGoogle Scholar
  41. Gregson AL, Oliveira G, Othoro C, Calvo-Calle JM, Thorton GB, Nardin E, Edelman R (2008) Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein. PLoS One 3(2):e1556PubMedGoogle Scholar
  42. Guerrero RA, Ball JM, Krater SS, Pacheco SE, Clements JD, Estes MK (2001) Recombinant Norwalk virus-like particles administered intranasally to mice induce systemic and mucosal (fecal and vaginal) immune responses. J Virol 75:9713–9722PubMedGoogle Scholar
  43. Guler R, Parihar SP, Spohn G, Johansen P, Brombacher F, Bachmann MF (2011) Blocking IL-1alpha but not IL-1beta increases susceptibility to chronic Mycobacterium tuberculosis infection in mice. Vaccine 29:1339–1346PubMedGoogle Scholar
  44. Hagensee ME, Yaegashi N, Galloway DA (1993) Self-assembly of human papillomavirus type 1 capsids by expression of the L1 protein alone or by coexpression of the L1 and L2 capsid proteins. J Virol 67:315–322PubMedGoogle Scholar
  45. Haney M, Kosten TR (2004) Therapeutic vaccines for substance dependence. Exp Rev Vac 3:11–18Google Scholar
  46. Harrington PR, Yount B, Johnston RE, Davis N, Moe C, Baric RS (2002) Systemic, mucosal, and heterotypic immune induction in mice inoculated with Venezuelan equine encephalitis replicons expressing Norwalk virus-like particles. J Virol 76:730–742PubMedGoogle Scholar
  47. Harris J, Keane J (2010) How tumour necrosis factor blockers interfere with tuberculosis immunity. Clin Exp Immunol 161:1–9PubMedGoogle Scholar
  48. Hoft DF, Leonardi C, Milligan T, Nahass GT, Kemp B, Cook S, Tennant J, Carey M (1999) Clinical reactogenicity of intradermal bacille Calmette-Guerin vaccination. Clin Infect Dis 28:785–790PubMedGoogle Scholar
  49. Holmgren J, Czerkinsky C (2005) Mucosal immunity and vaccines. Nat Med 11:S45–S53PubMedGoogle Scholar
  50. Iwasaki A, Medzhitov R (2010) Regulation of adaptive immunity by the innate immune system. Science 327:291–295PubMedGoogle Scholar
  51. Jegerlehner A, Tissot A, Lechner F, Sebbel P, Erdmann I, Kundig T, Bachi T, Storni T, Jennings G, Pumpens P, Renner WA, Bachmann MF (2002) A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses. Vaccine 20:3104–3112PubMedGoogle Scholar
  52. Jegerlehner A, Schmitz N, Storni T, Bachmann MF (2004) Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. J Immunol 172:5598–5605PubMedGoogle Scholar
  53. Jennings GT, Bachmann MF (2009) Immunodrugs: therapeutic VLP-based vaccines for chronic diseases. Annu Rev Pharmacol Toxicol 49:303–326PubMedGoogle Scholar
  54. Johansen P, Storni T, Rettig L, Qiu Z, Der-Sarkissian A, Smith KA, Manolova V, Lang KS, Senti G, Mullhaupt B, Gerlach T, Speck RF, Bot A, Kundig TM (2008) Antigen kinetics determines immune reactivity. Proc Natl Acad Sci USA 105:5189–5194PubMedGoogle Scholar
  55. Kang SM, Compans RW (2003) Enhancement of mucosal immunization with virus-like particles of simian immunodeficiency virus. J Virol 77:3615–3623PubMedGoogle Scholar
  56. Kang SM, Song JM, Quan FS, Compans RW (2009) Influenza vaccines based on virus-like particles. Virus Res 143:140–146PubMedGoogle Scholar
  57. Kao JH, Chen DS (2002) Global control of hepatitis B virus infection. Lancet Infect Dis 2:395–403PubMedGoogle Scholar
  58. Kemp TJ, Hildesheim A, Safaeian M, Dauner JG, Pan Y, Porras C, Schiller JT, Lowy DR, Herrero R, Pinto LA (2011) HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection. Vaccine 29:2011–2014PubMedGoogle Scholar
  59. Kirnbauer R, Booy F, Cheng N, Lowy DR, Schiller JT (1992) Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci USA 89:12180–12184PubMedGoogle Scholar
  60. Klamp T, Schumacher J, Huber G, Kuhne C, Meissner U, Selmi A, Hiller T, Kreiter S, Markl J, Tureci O, Sahin U (2011) Highly specific auto-antibodies against claudin-18 isoform 2 induced by a chimeric HBcAg virus-like particle vaccine kill tumor cells and inhibit the growth of lung metastases. Cancer Res 71:516–527PubMedGoogle Scholar
  61. Kleid DG, Yansura D, Small B, Dowbenko D, Moore DM, Grubman MJ, McKercher PD, Morgan DO, Robertson BH, Bachrach HL (1981) Cloned viral protein vaccine for foot-and-mouth disease: responses in cattle and swine. Science 214:1125–1129PubMedGoogle Scholar
  62. Klein U, Dalla-Favera R (2008) Germinal centres: role in B-cell physiology and malignancy. Nat Rev Immunol 8:22–33PubMedGoogle Scholar
  63. Klimek L, Willers J, Hammann-Haenni A, Pfaar O, Stocker H, Mueller P, Renner WA, Bachmann MF (2011) Assessment of clinical efficacy of CYT003-QbG10 in patients with allergic rhinoconjunctivitis: a phase IIb study. Clin Exp Allergy 41:1305–1312PubMedGoogle Scholar
  64. Klinman DM (2006) Adjuvant activity of CpG oligodeoxynucleotides. Int Rev Immunol 25:135–154PubMedGoogle Scholar
  65. Lambert LC, Fauci AS (2010) Influenza vaccines for the future. N Engl J Med 363:2036–2044PubMedGoogle Scholar
  66. Li Q, Cao C, Chackerian B, Schiller J, Gordon M, Ugen KE, Morgan D (2004) Overcoming antigen masking of anti-amyloidbeta antibodies reveals breaking of B cell tolerance by virus-like particles in amyloidbeta immunized amyloid precursor protein transgenic mice. BMC Neurosci 5:21PubMedGoogle Scholar
  67. Link A, Bachmann MF (2010) Immunodrugs: breaking B- but not T-cell tolerance with therapeutic anticytokine vaccines. Immunotherapy 2:561–574PubMedGoogle Scholar
  68. Ma Y, Ma AG, Peng Z (2007) A potential immunotherapy approach: mucosal immunization with an IL-13 peptide-based virus-like particle vaccine in a mouse asthma model. Vaccine 25:8091–8099PubMedGoogle Scholar
  69. 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 38:1404–1413PubMedGoogle Scholar
  70. Martin SJ, Vyakarnam A, Cheingsong-Popov R, Callow D, Jones KL, Senior JM, Adams SE, Kingsman AJ, Matear P, Gotch FM et al (1993) Immunization of human HIV-seronegative volunteers with recombinant p17/p24:Ty virus-like particles elicits HIV-1 p24-specific cellular and humoral immune responses. AIDS 7:1315–1323PubMedGoogle Scholar
  71. Mason HS, Ball JM, Shi JJ, Jiang X, Estes MK, Arntzen CJ (1996) Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice. Proc Natl Acad Sci USA 93:5335–5340PubMedGoogle Scholar
  72. Maurer P, Bachmann MF (2010) Immunization against angiotensins for the treatment of hypertension. Clin Immunol 134:89–95PubMedGoogle Scholar
  73. Maurer P, Jennings GT, Willers J, Rohner F, Lindman Y, Roubicek K, Renner WA, Muller P, Bachmann MF (2005) A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity. Eur J Immunol 35:2031–2040PubMedGoogle Scholar
  74. McGinnes LW, Gravel KA, Finberg RW, Kurt-Jones EA, Massare MJ, Smith G, Schmidt MR, Morrison TG (2011) Assembly and immunological properties of Newcastle disease virus-like particles containing the respiratory syncytial virus F and G proteins. J Virol 85:366–377PubMedGoogle Scholar
  75. Meylan E, Tschopp J (2006) Toll-like receptors and RNA helicases: two parallel ways to trigger antiviral responses. Mol Cell 22:561–569PubMedGoogle Scholar
  76. Minor P (2009) Vaccine-derived poliovirus (VDPV): impact on poliomyelitis eradication. Vaccine 27:2649–2652PubMedGoogle Scholar
  77. Moorthy V, Reed Z, Smith PG (2007) Measurement of malaria vaccine efficacy in phase III trials: report of a WHO consultation. Vaccine 25:5115–5123PubMedGoogle Scholar
  78. Morens DM, Folkers GK, Fauci AS (2004) The challenge of emerging and re-emerging infectious diseases. Nature 430:242–249PubMedGoogle Scholar
  79. Murawski MR, McGinnes LW, Finberg RW, Kurt-Jones EA, Massare MJ, Smith G, Heaton PM, Fraire AE, Morrison TG (2010) Newcastle disease virus-like particles containing respiratory syncytial virus G protein induced protection in Balb/c mice, with no evidence of immunopathology. J Virol 84:1110–1123PubMedGoogle Scholar
  80. Nardin EH, Oliveira GA, Calvo-Calle JM, Wetzel K, Maier C, Birkett AJ, Sarpotdar P, Corado ML, Thornton GB, Schmidt A (2004) Phase I testing of a malaria vaccine composed of hepatitis B virus core particles expressing Plasmodium falciparum circumsporozoite epitopes. Infect Immun 72(11):6519–6527PubMedGoogle Scholar
  81. Neirynck S, Deroo T, Saelens X, Vanlandschoot P, Jou WM, Fiers W (1999) A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat Med 5:1157–1163PubMedGoogle Scholar
  82. Nicollier-Jamot B, Ogier A, Piroth L, Pothier P, Kohli E (2004) Recombinant virus-like particles of a norovirus (genogroup II strain) administered intranasally and orally with mucosal adjuvants LT and LT(R192G) in BALB/c mice induce specific humoral and cellular Th1/Th2-like immune responses. Vaccine 22:1079–1086PubMedGoogle Scholar
  83. Noad R, Roy P (2003) Virus-like particles as immunogens. Trends Microbiol 11:438–444PubMedGoogle Scholar
  84. Nussenzweig V, Nussenzweig R (1986) Experimental basis for the development of a synthetic vaccine against Plasmodium falciparum malaria sporozoites. CIBA Found Symp 119:150–163PubMedGoogle Scholar
  85. Oliveira GA, Wetzel K, Calvo-Calle JM, Nussenzweig R, Schmidt A, Birkett A, Dubovsky F, Tierney E, Gleiter CH, Boehmer G, Luty AJ, Ramharter M, Thornton GB, Kremsner PG, Nardin EH (2005) Safety and enhanced immunogenicity of a hepatitis B core particle Plasmodium falciparum malaria vaccine formulated in adjuvant Montanide ISA 720 in a phase I trial. Infect Immun 73:3587–3597PubMedGoogle Scholar
  86. Patel MM, Hall AJ, Vinje J, Parashar UD (2009) Noroviruses: a comprehensive review. J Clin Virol 44:1–8PubMedGoogle Scholar
  87. Peters BS, Cheingsong-Popov R, Callow D, Foxall R, Patou G, Hodgkin K, Weber JN (1997) A pilot phase II study of the safety and immunogenicity of HIV p17/p24:VLP (p24-VLP) in asymptomatic HIV seropositive subjects. J Infect 35:231–235PubMedGoogle Scholar
  88. Pinto LA, Edwards J, Castle PE, Harro CD, Lowy DR, Schiller JT, Wallace D, Kopp W, Adelsberger JW, Baseler MW, Berzofsky JA, Hildesheim A (2003) Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles. J Infect Dis 188:327–338PubMedGoogle Scholar
  89. Pumpens P, Grens E (2001) HBV core particles as a carrier for B cell/T cell epitopes. Intervirology 44:98–114PubMedGoogle Scholar
  90. Regules JA, Cummings JF, Ockenhouse CF (2011) The RTS, S vaccine candidate for malaria. Exp Rev Vac 10:589–599Google Scholar
  91. Ren S, Fengyu ZS, Zhao M, Wang X, Wang X, Chen Y, Wu Z, Ren Z (2011) Inhibition of tumor angiogenesis in lung cancer by T4 phage surface displaying mVEGFR2 vaccine. Vaccine 29:5802–5811PubMedGoogle Scholar
  92. Roden RB, Yutzy WHt, Fallon R, Inglis S, Lowy DR, Schiller JT (2000) Minor capsid protein of human genital papillomaviruses contains subdominant, cross-neutralizing epitopes. Virology 270:254–257PubMedGoogle Scholar
  93. Rohn TA, Bachmann MF (2010) Vaccines against non-communicable diseases. Curr Opin Immunol 22:391–396PubMedGoogle Scholar
  94. Rohn TA, Jennings GT, Hernandez M, Grest P, Beck M, Zou Y, Kopf M, Bachmann MF (2006) Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis. Eur J Immunol 36:2857–2867PubMedGoogle Scholar
  95. Rose RC, Bonnez W, Reichman RC, Garcea RL (1993) Expression of human papillomavirus type 11 L1 protein in insect cells: in vivo and in vitro assembly of viruslike particles. J Virol 67:1936–1944PubMedGoogle Scholar
  96. Santi L, Batchelor L, Huang Z, Hjelm B, Kilbourne J, Arntzen CJ, Chen Q, Mason HS (2008) An efficient plant viral expression system generating orally immunogenic Norwalk virus-like particles. Vaccine 26:1846–1854PubMedGoogle Scholar
  97. Schiller JT, Castellsague X, Villa LL, Hildesheim A (2008) An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine 26(Suppl 10):K53–K61PubMedGoogle Scholar
  98. Schlender J, Bossert B, Buchholz U, Conzelmann KK (2000) Bovine respiratory syncytial virus nonstructural proteins NS1 and NS2 cooperatively antagonize alpha/beta interferon-induced antiviral response. J Virol 74:8234–8242PubMedGoogle Scholar
  99. Sekaly RP (2008) The failed HIV Merck vaccine study: a step back or a launching point for future vaccine development? J Exp Med 205:7–12PubMedGoogle Scholar
  100. Shi W, Liu J, Huang Y, Qiao L (2001) Papillomavirus pseudovirus: a novel vaccine to induce mucosal and systemic cytotoxic T-lymphocyte responses. J Virol 75:10139–10148PubMedGoogle Scholar
  101. Shirato H (2011) Norovirus and histo-blood group antigens. Jpn J Infect Dis 64:95–103PubMedGoogle Scholar
  102. Smith D, Gow I, Colebunders R, Weller I, Tchamouroff S, Weber J, Boag F, Hales G, Adams S, Patou G, Cooper DA (2001) Therapeutic vaccination (p24-VLP) of patients with advanced HIV-1 infection in the pre-HAART era does not alter CD4 cell decline. HIV Med 2:272–275PubMedGoogle Scholar
  103. Smith JF, Brownlow M, Brown M, Kowalski R, Esser MT, Ruiz W, Barr E, Brown DR, Bryan JT (2007) Antibodies from women immunized with Gardasil cross-neutralize HPV 45 pseudovirions. HumVaccin 3:109–115Google Scholar
  104. Sonderegger I, Rohn TA, Kurrer MO, Iezzi G, Zou Y, Kastelein RA, Bachmann MF, Kopf M (2006) Neutralization of IL-17 by active vaccination inhibits IL-23-dependent autoimmune myocarditis. Eur J Immunol 36:2849–2856PubMedGoogle Scholar
  105. Speiser DE, Schwarz K, Baumgaertner P, Manolova V, Devevre E, Sterry W, Walden P, Zippelius A, Conzett KB, Senti G, Voelter V, Cerottini JP, Guggisberg D, Willers J, Geldhof C, Romero P, Kundig T, Knuth A, Dummer R, Trefzer U, Bachmann MF (2010) Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients. J Immunother 33:848–858PubMedGoogle Scholar
  106. Spohn G, Schwarz K, Maurer P, Illges H, Rajasekaran N, Choi Y, Jennings GT, Bachmann MF (2005) Protection against osteoporosis by active immunization with TRANCE/RANKL displayed on virus-like particles. J Immunol 175:6211–6218PubMedGoogle Scholar
  107. Spohn G, Guler R, Johansen P, Keller I, Jacobs M, Beck M, Rohner F, Bauer M, Dietmeier K, Kundig TM, Jennings GT, Brombacher F, Bachmann MF (2007) A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis. J Immunol 178:7450–7457PubMedGoogle Scholar
  108. Spohn G, Keller I, Beck M, Grest P, Jennings GT, Bachmann MF (2008) Active immunization with IL-1 displayed on virus-like particles protects from autoimmune arthritis. Eur J Immunol 38:877–887PubMedGoogle Scholar
  109. Suzich JA, Ghim SJ, Palmer-Hill FJ, White WI, Tamura JK, Bell JA, Newsome JA, Jenson AB, Schlegel R (1995) Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas. Proc Natl Acad Sci USA 92:11553–11557PubMedGoogle Scholar
  110. Tacket CO, Mason HS, Losonsky G, Estes MK, Levine MM, Arntzen CJ (2000) Human immune responses to a novel Norwalk virus vaccine delivered in transgenic potatoes. J Infect Dis 182(1):302–305PubMedGoogle Scholar
  111. Tacket CO, Sztein MB, Losonsky GA, Wasserman SS, Estes MK (2003) Humoral, mucosal, and cellular immune responses to oral Norwalk virus-like particles in volunteers. Clin Immunol 108:241–247PubMedGoogle Scholar
  112. Tegerstedt K, Lindencrona JA, Curcio C, Andreasson K, Tullus C, Forni G, Dalianis T, Kiessling R, Ramqvist T (2005) A single vaccination with polyomavirus VP1/VP2Her2 virus-like particles prevents outgrowth of HER-2/neu-expressing tumors. Cancer Res 65:5953–5957PubMedGoogle Scholar
  113. The RTS SCTP (2011) First results of phase 3 trial of RTS, S/AS01 malaria vaccine in African children. N Engl J Med 365:1863–1875Google Scholar
  114. Tissot AC, Maurer P, Nussberger J, Sabat R, Pfister T, Ignatenko S, Volk HD, Stocker H, Muller P, Jennings GT, Wagner F, Bachmann MF (2008) Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study. Lancet 371:821–827PubMedGoogle Scholar
  115. Tissot AC, Renhofa R, Schmitz N, Cielens I, Meijerink E, Ose V, Jennings GT, Saudan P, Pumpens P, Bachmann MF (2010) Versatile virus-like particle carrier for epitope based vaccines. PLoS One 5:e9809PubMedGoogle Scholar
  116. Vafaie J, Schwartz RA (2004) Parvovirus B19 infections. Int J Dermatol 43:747–749PubMedGoogle Scholar
  117. Villadangos JA, Shortman K (2008) Found in translation: the human equivalent of mouse CD8+ dendritic cells. J Exp Med 207:1131–1134Google Scholar
  118. Walther M, Dunachie S, Keating S, Vuola JM, Berthoud T, Schmidt A, Maier C, Andrews L, Andersen RF, Gilbert S, Poulton I, Webster D, Dubovsky F, Tierney E, Sarpotdar P, Correa S, Huntcooke A, Butcher G, Williams J, Sinden RE, Thornton GB, Hill AV (2005) Safety, immunogenicity and efficacy of a pre-erythrocytic malaria candidate vaccine, ICC-1132 formulated in Seppic ISA 720. Vaccine 23:857–864PubMedGoogle Scholar
  119. Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC (2003) Predominant autoantibody production by early human B cell precursors. Science 301:1374–1377PubMedGoogle Scholar
  120. WHO Consultative Group (1982) The relation between acute persisting spinal paralysis and poliomyelitis vaccine–results of a ten-year enquiry. Bull World Health Organ 60:231–242Google Scholar
  121. Wiessner C, Wiederhold KH, Tissot AC, Frey P, Danner S, Jacobson LH, Jennings GT, Luond R, Ortmann R, Reichwald J, Zurini M, Mir A, Bachmann MF, Staufenbiel M (2011) The second-generation active A{beta} immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. J Neurosci 31:9323–9331PubMedGoogle Scholar
  122. Xia M, Farkas T, Jiang X (2007) Norovirus capsid protein expressed in yeast forms virus-like particles and stimulates systemic and mucosal immunity in mice following an oral administration of raw yeast extracts. J Med Virol 79:74–83PubMedGoogle Scholar
  123. Xiao S, Kumar M, Yang X, Akkoyunlu M, Collins PL, Samal SK, Pal U (2011) A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen. Vaccine 29:5294–5303PubMedGoogle Scholar
  124. Yin Y, Li H, Wu S, Dong D, Zhang J, Fu L, Xu J, Chen W (2011) Hepatitis B virus core particles displaying Mycobacterium tuberculosis antigen ESAT-6 enhance ESAT-6-specific immune responses. Vaccine 29:5645–5651PubMedGoogle Scholar
  125. Zamora E, Handisurya A, Shafti-Keramat S, Borchelt D, Rudow G, Conant K, Cox C, Troncoso JC, Kirnbauer R (2006) Papillomavirus-like particles are an effective platform for amyloid-beta immunization in rabbits and transgenic mice. J Immunol 177:2662–2670PubMedGoogle Scholar
  126. Zanetti AR, Van Damme P, Shouval D (2008) The global impact of vaccination against hepatitis B: a historical overview. Vaccine 26:6266–6273PubMedGoogle Scholar
  127. Zhang X, Buehner NA, Hutson AM, Estes MK, Mason HS (2006) Tomato is a highly effective vehicle for expression and oral immunization with Norwalk virus capsid protein. Plant Biotechnol J 4(4):419–432PubMedGoogle Scholar
  128. Zhou J, Sun XY, Stenzel DJ, Frazer IH (1991) Expression of vaccinia recombinant HPV 16 L1 and L2 ORF proteins in epithelial cells is sufficient for assembly of HPV virion-like particles. Virology 185(1):251–257PubMedGoogle Scholar
  129. Zhou W, Bi J, Janson JC, Li Y, Huang Y, Zhang Y, Su Z (2006) Molecular characterization of recombinant Hepatitis B surface antigen from Chinese hamster ovary and Hansenula polymorpha cells by high-performance size exclusion chromatography and multi-angle laser light scattering. J Chromatogr 838(2):71–77Google Scholar
  130. Zou Y, Sonderegger I, Lipowsky G, Jennings GT, Schmitz N, Landi M, Kopf M, Bachmann MF (2010) Combined vaccination against IL-5 and eotaxin blocks eosinophilia in mice. Vaccine 28(18):3192–3200PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Cytos Biotechnology AGSchlierenSwitzerland
  2. 2.DermatologyUniversity HospitalZürichSwitzerland

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