Poxviruses pp 311-327 | Cite as

Recombinant poxvirus vaccines in biomedical research

  • Barbara S. Schnierle
  • Yasemin Suezer
  • Gerd Sutter
Part of the Birkhäuser Advances in Infectious Diseases book series (BAID)


In biomedical research recombinant poxviruses are investigated as important candidate medicines to derive advanced options for prevention and/or treatment of infectious diseases or cancer. Genetically engineered viruses can readily synthesize biologically active heterologous proteins, serve to determine relevant targets of cell-mediated and humoral immunity, and identify types of immune responses needed for protection against a multitude of different specific diseases. Substantial progress in vaccine development is based on the availability of exceptionally safe but efficient carrier viruses, on increasingly versatile vector technologies and on the feasibility of large scale manufacturing. Moreover, advances in deciphering the molecular pathways regulating poxvirus-host interactions will provide additional means to potently activate innate immune stimulation upon vaccination and to derive vectors with specifically targeted replicative capacity for experimental tumor therapy.


Human Immunodeficiency Virus Vaccinia Virus Recombinant Vaccinia Virus Rabbit Hemorrhagic Disease Virus Myxoma Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Moss B, Carroll MW, Wyatt LS, Bennink JR, Hirsch VM, Goldstein S, Elkins WR, Fuerst TR, Lifson JD, Piatak M et al (1996) Host range restricted, non-replicating vaccinia virus vectors as vaccine candidates. Adv Exp Med Biol 397: 7–13PubMedGoogle Scholar
  2. 2.
    Paoletti E (1996) Applications of pox virus vectors to vaccination: an update. Proc Natl Acad Sci USA 93: 11349–11353PubMedGoogle Scholar
  3. 3.
    Tartaglia J, Perkus ME, Taylor J, Norton EK, Audonnet JC, Cox WI, Davis SW, van der HJ, Meignier B, Riviere M (1992) NYVAC: a highly attenuated strain of vaccinia virus.Virology 188: 217–232PubMedGoogle Scholar
  4. 4.
    Sutter G, Moss B (1992) Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc Natl Acad Sci USA 89: 10847–10851PubMedGoogle Scholar
  5. 5.
    Drexler I, Staib C, Sutter G (2004) Modified vaccinia virus Ankara as antigen delivery system: how can we best use its potential? Curr Opin Biotechnol 15: 506–512PubMedGoogle Scholar
  6. 6.
    Franchini G, Gurunathan S, Baglyos L, Plotkin S, Tartaglia J (2004) Poxvirusbased vaccine candidates for HIV: two decades of experience with special emphasis on canarypox vectors. Expert Rev Vaccines 3: S75–S88PubMedGoogle Scholar
  7. 7.
    Smith GL, Mackett M, Moss B (1983) Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen. Nature 302: 490–495PubMedGoogle Scholar
  8. 8.
    Panicali D, Davis SW, Weinberg RL, Paoletti E (1983) Construction of live vaccines by using genetically engineered poxviruses: biological activity of recombinant vaccinia virus expressing influenza virus hemagglutinin. Proc Natl Acad Sci USA 80: 5364–5368PubMedGoogle Scholar
  9. 9.
    Boyle DB, Coupar BE (1988) Construction of recombinant fowlpox viruses as vectors for poultry vaccines. Virus Res 10: 343–356PubMedGoogle Scholar
  10. 10.
    Taylor J, Paoletti E (1988) Fowlpox virus as a vector in non-avian species. Vaccine 6: 466–468PubMedGoogle Scholar
  11. 11.
    Fischer T, Planz O, Stitz L, Rziha HJ (2003) Novel recombinant parapoxvirus vectors induce protective humoral and cellular immunity against lethal herpesvirus challenge infection in mice. J Virol 77: 9312–9323PubMedGoogle Scholar
  12. 12.
    Marsland BJ, Tisdall DJ, Heath DD, Mercer AA (2003) Construction of a recombinant orf virus that expresses an Echinococcus granulosus vaccine antigen from a novel genomic insertion site. Arch Virol 148: 555–562PubMedGoogle Scholar
  13. 13.
    Tripathy DN (1999) Swinepox virus as a vaccine vector for swine pathogens. Adv Vet Med 41: 463–480PubMedGoogle Scholar
  14. 14.
    Romero CH, Barrett T, Chamberlain RW, Kitching RP, Fleming M, Black DN (1994) Recombinant capripoxvirus expressing the hemagglutinin protein gene of rinderpest virus: protection of cattle against rinderpest and lumpy skin disease viruses. Virology 204: 425–429PubMedGoogle Scholar
  15. 15.
    Kerr PJ, Jackson RJ (1995) Myxoma virus as a vaccine vector for rabbits: antibody levels to influenza virus haemagglutinin presented by a recombinant myxoma virus. Vaccine 13: 1722–1726PubMedGoogle Scholar
  16. 16.
    Bertagnoli S, Gelfi J, Le Gall G, Boilletot E, Vautherot JF, Rasschaert D, Laurent S, Petit F, Boucraut-Baralon C, Milon A (1996) Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein. J Virol 70: 5061–5066PubMedGoogle Scholar
  17. 17.
    Moss B (2001) Poxviridae: The viruses and their replication. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman BE (eds): Fields Virology, vol. 2. Lippincott Williams & Wilkins, Philadelphia, 2849–2883Google Scholar
  18. 18.
    Mackett M, Smith GL, Moss B (1984) General method for production and selection of infectious vaccinia virus recombinants expressing foreign genes. J Virol 49: 857–864PubMedGoogle Scholar
  19. 19.
    Wyatt LS, Shors ST, Murphy BR, Moss B (1996) Development of a replicationdeficient recombinant vaccinia virus vaccine effective against parainfluenza virus 3 infection in an animal model. Vaccine 14: 1451–1458PubMedGoogle Scholar
  20. 20.
    Chakrabarti S, Sisler JR, Moss B (1997) Compact, synthetic, vaccinia virus early/late promoter for protein expression. Biotechniques 23: 1094–1097PubMedGoogle Scholar
  21. 21.
    Holzer GW, Mayrhofer J, Gritschenberger W, Falkner FG (2005) Dominant negative selection of vaccinia virus using a thymidine kinase/thymidylate kinase fusion gene and the prodrug azidothymidine. Virology 337: 235–241PubMedGoogle Scholar
  22. 22.
    Chakrabarti S, Brechling K, Moss B (1985) Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. Mol Cell Biol 5: 3403–3409PubMedGoogle Scholar
  23. 23.
    Carroll MW, Moss B (1995) E. coli beta-glucuronidase (GUS) as a marker for recombinant vaccinia viruses. Biotechniques 19: 352–354, 356PubMedGoogle Scholar
  24. 24.
    Falkner FG, Moss B (1988) Escherichia coli gpt gene provides dominant selection for vaccinia virus open reading frame expression vectors. J Virol 62: 1849–1854PubMedGoogle Scholar
  25. 25.
    Perkus ME, Limbach K, Paoletti E (1989) Cloning and expression of foreign genes in vaccinia virus, using a host range selection system. J Virol 63: 3829–3836PubMedGoogle Scholar
  26. 26.
    Blasco R, Moss B (1995) Selection of recombinant vaccinia viruses on the basis of plaque formation. Gene 158: 157–162PubMedGoogle Scholar
  27. 27.
    Sanchez-Puig JM, Blasco R (2005) Isolation of vaccinia MVA recombinants using the viral F13L gene as the selective marker. Biotechniques 39: 665–666, 668, 670PubMedGoogle Scholar
  28. 28.
    Holzer GW, Gritschenberger W, Mayrhofer JA, Wieser V, Dorner F, Falkner FG (1998) Dominant host range selection of vaccinia recombinants by rescue of an essential gene. Virology 249: 160–166PubMedGoogle Scholar
  29. 29.
    Sutter G, Ramsey-Ewing A, Rosales R, Moss B (1994) Stable expression of the vaccinia virus K1L gene in rabbit cells complements the host range defect of a vaccinia virus mutant. J Virol 68: 4109–4116PubMedGoogle Scholar
  30. 30.
    Staib C, Drexler I, Ohlmann M, Wintersperger S, Erfle V, Sutter G (2000) Transient host range selection for genetic engineering of modified vaccinia virus Ankara. Biotechniques 28: 1137–1142PubMedGoogle Scholar
  31. 31.
    Staib C, Lowel M, Erfle V, Sutter G (2003) Improved host range selection for recombinant modified vaccinia virus Ankara. Biotechniques 34: 694–696PubMedGoogle Scholar
  32. 32.
    Scheiflinger F, Dorner F, Falkner FG (1992) Construction of chimeric vaccinia viruses by molecular cloning and packaging. Proc Natl Acad Sci USA 89: 9977–9981PubMedGoogle Scholar
  33. 33.
    Yao XD, Evans DH (2003) High-frequency genetic recombination and reactivation of orthopoxviruses from DNA fragments transfected into leporipoxvirus-infected cells. J Virol 77: 7281–7290PubMedGoogle Scholar
  34. 34.
    Merchlinsky M, Moss B (1992) Introduction of foreign DNA into the vaccinia virus genome by in vitro ligation: recombination-independent selectable cloning vectors. Virology 190: 522–526PubMedGoogle Scholar
  35. 35.
    Pfleiderer M, Falkner FG, Dorner F (1995) A novel vaccinia virus expression system allowing construction of recombinants without the need for selection markers, plasmids and bacterial hosts. J Gen Virol 76: 2957–2962PubMedGoogle Scholar
  36. 36.
    Smith ES, Shi S, Zauderer M (2004) Construction of cDNA libraries in vaccinia virus. Methods Mol Biol 269: 65–76PubMedGoogle Scholar
  37. 37.
    Domi A, Moss B (2005) Engineering of a vaccinia virus bacterial artificial chromosome in Escherichia coli by bacteriophage lambda-based recombination. Nat Methods 2: 95–97PubMedGoogle Scholar
  38. 38.
    Smith GL, Murphy BR, Moss B (1983) Construction and characterization of an infectious vaccinia virus recombinant that expresses the influenza hemagglutinin gene and induces resistance to influenza virus infection in hamsters. Proc Natl Acad Sci USA 80: 7155–7159PubMedGoogle Scholar
  39. 39.
    Kieny MP, Lathe R, Drillien R, Spehner D, Skory S, Schmitt D, Wiktor T, Koprowski H, Lecocq JP (1984) Expression of rabies virus glycoprotein from a recombinant vaccinia virus. Nature 312: 163–166PubMedGoogle Scholar
  40. 40.
    Perez-Jimenez E, Kochan G, Gherardi MM, Esteban M (2006) MVA-LACK as a safe and efficient vector for vaccination against leishmaniasis. Microbes Infect 8: 810–822PubMedGoogle Scholar
  41. 41.
    Minke JM, Fischer L, Baudu P, Guigal PM, Sindle T, Mumford JA, Audonnet JC (2006) Use of DNA and recombinant canarypox viral (ALVAC) vectors for equine herpes virus vaccination. Vet Immunol Immunopathol 111: 47–57PubMedGoogle Scholar
  42. 42.
    Henkel M, Planz O, Fischer T, Stitz L, Rziha HJ (2005) Prevention of virus persistence and protection against immunopathology after Borna disease virus infection of the brain by a novel Orf virus recombinant. J Virol 79: 314–325PubMedGoogle Scholar
  43. 43.
    Karaca K, Swayne DE, Grosenbaugh D, Bublot M, Robles A, Spackman E, Nordgren R (2005) Immunogenicity of fowlpox virus expressing the avian influenza virus H5 gene (TROVAC AIV-H5) in cats. Clin Diagn Lab Immunol 12: 1340–1342PubMedGoogle Scholar
  44. 44.
    Mencher JS, Smith SR, Powell TD, Stinchcomb DT, Osorio JE, Rocke TE (2004) Protection of black-tailed prairie dogs (Cynomys ludovicianus) against plague after voluntary consumption of baits containing recombinant raccoon poxvirus vaccine. Infect Immun 72: 5502–5505PubMedGoogle Scholar
  45. 45.
    Breathnach CC, Clark HJ, Clark RC, Olsen CW, Townsend HG, Lunn DP (2006) Immunization with recombinant modified vaccinia Ankara (rMVA) constructs encoding the HA or NP gene protects ponies from equine influenza virus challenge. Vaccine 24: 1180–1190PubMedGoogle Scholar
  46. 46.
    Paillot R, Ellis SA, Daly JM, Audonnet JC, Minke JM, Davis-Poynter N, Hannant D, Kydd JH (2006) Characterisation of CTL and IFN-gamma synthesis in ponies following vaccination with a NYVAC-based construct coding for EHV-1 immediate early gene, followed by challenge infection. Vaccine 24: 1490–1500PubMedGoogle Scholar
  47. 47.
    Girard MP, Osmanov SK, Kieny MP (2006) A review of vaccine research and development: The human immunodeficiency virus (HIV). Vaccine 24: 4062–4081PubMedGoogle Scholar
  48. 48.
    Wyatt LS, Earl PL, Liu JY, Smith JM, Montefiori DC, Robinson HL, Moss B (2004) Multiprotein HIV type 1 clade B DNA and MVA vaccines: construction, expression, and immunogenicity in rodents of the MVA component. AIDS Res Hum Retroviruses 20: 645–653PubMedGoogle Scholar
  49. 49.
    De Rose R, Chea S, Dale CJ, Reece J, Fernandez CS, Wilson KM, Thomson S, Ramshaw IA, Coupar BE, Boyle DB et al (2005) Subtype AE HIV-1 DNA and recombinant Fowlpoxvirus vaccines encoding five shared HIV-1 genes: safety and T cell immunogenicity in macaques. Vaccine 23: 1949–1956PubMedGoogle Scholar
  50. 50.
    Goonetilleke N, Moore S, Dally L, Winstone N, Cebere I, Mahmoud A, Pinheiro S, Gillespie G, Brown D, Loach V et al (2006) Induction of multifunctional human immunodeficiency virus type 1 (HIV-1)-specific T cells capable of proliferation in healthy subjects by using a prime-boost regimen of DNAand modified vaccinia virus Ankara-vectored vaccines expressing HIV-1 gag coupled to CD8+ T-cell epitopes. J Virol 80: 4717–4728PubMedGoogle Scholar
  51. 51.
    Sutter G, Staib C (2003) Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery. Curr Drug Targets Infect Disord 3: 263–271PubMedGoogle Scholar
  52. 52.
    Im EJ, Hanke T (2004) MVA as a vector for vaccines against HIV-1. Expert Rev Vaccines 3: S89–S97PubMedGoogle Scholar
  53. 53.
    Skinner MA, Laidlaw SM, Eldaghayes I, Kaiser P, Cottingham MG (2005) Fowlpox virus as a recombinant vaccine vector for use in mammals and poultry. Expert Rev Vaccines 4: 63–76PubMedGoogle Scholar
  54. 54.
    Gherardi MM, Esteban M (2005) Recombinant poxviruses as mucosal vaccine vectors. J Gen Virol 86: 2925–2936PubMedGoogle Scholar
  55. 55.
    Coupar BE, Purcell DF, Thomson SA, Ramshaw IA, Kent SJ, Boyle DB (2006) Fowlpox virus vaccines for HIV and SHIV clinical and pre-clinical trials. Vaccine 24: 1378–1388PubMedGoogle Scholar
  56. 56.
    Douek DC, Kwong PD, Nabel GJ (2006) The rational design of an AIDS vaccine. Cell 124: 677–681PubMedGoogle Scholar
  57. 57.
    Earl PL, Wyatt LS, Montefiori DC, Bilska M, Woodward R, Markham PD, Malley JD, Vogel TU, Allen TM, Watkins DI et al (2002) Comparison of vaccine strategies using recombinant env-gag-pol MVA with or without an oligomeric Env protein boost in the SHIV rhesus macaque model. Virology 294: 270–281PubMedGoogle Scholar
  58. 58.
    Quinnan GV Jr, Yu XF, Lewis MG, Zhang PF, Sutter G, Silvera P, Dong M, Choudhary A, Sarkis PT, Bouma P et al (2005) Protection of rhesus monkeys against infection with minimally pathogenic simian-human immunodeficiency virus: correlations with neutralizing antibodies and cytotoxic T cells. J Virol 79: 3358–3369PubMedGoogle Scholar
  59. 59.
    Shepard CW, Finelli L, Alter MJ (2005) Global epidemiology of hepatitis C virus infection. Lancet Infect Dis 5: 558–567PubMedGoogle Scholar
  60. 60.
    Abraham JD, Himoudi N, Kien F, Berland JL, Codran A, Bartosch B, Baumert T, Paranhos-Baccala G, Schuster C, Inchauspe G, Kieny MP (2004) Comparative immunogenicity analysis of modified vaccinia Ankara vectors expressing native or modified forms of hepatitis C virus E1 and E2 glycoproteins. Vaccine 22: 3917–3928PubMedGoogle Scholar
  61. 61.
    Pancholi P, Perkus M, Tricoche N, Liu Q, Prince AM (2003) DNA immunization with hepatitis C virus (HCV) polycistronic genes or immunization by HCV DNA priming-recombinant canarypox virus boosting induces immune responses and protection from recombinant HCV-vaccinia virus infection in HLA-A2.1-transgenic mice. J Virol 77: 382–390PubMedGoogle Scholar
  62. 62.
    Bisht H, Roberts A, Vogel L, Bukreyev A, Collins PL, Murphy BR, Subbarao K, Moss B (2004) Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Proc Natl Acad Sci USA 101: 6641–6646PubMedGoogle Scholar
  63. 63.
    Chen Z, Zhang L, Qin C, Ba L, Yi CE, Zhang F, Wei Q, He T, Yu W, Yu J et al (2005) Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. J Virol 79: 2678–2688PubMedGoogle Scholar
  64. 64.
    Xing Z, Santosuosso M, McCormick S, Yang TC, Millar J, Hitt M, Wan Y, Bramson J, Vordermeier HM (2005) Recent advances in the development of adenovirus-and poxvirus-vectored tuberculosis vaccines. Curr Gene Ther 5: 485–492PubMedGoogle Scholar
  65. 65.
    Moore AC, Hill AV (2004) Progress in DNA-based heterologous prime-boost immunization strategies for malaria. Immunol Rev 199: 126–143PubMedGoogle Scholar
  66. 66.
    Kumar P, Amara RR, Challu VK, Chadda VK, Satchidanandam V (2003) The Apa protein of Mycobacterium tuberculosis stimulates gamma interferonsecreting CD4+ and CD8+ T cells from purified protein derivative-positive individuals and affords protection in a guinea pig model. Infect Immun 71: 1929–1937PubMedGoogle Scholar
  67. 67.
    Goonetilleke NP, McShane H, Hannan CM, Anderson RJ, Brookes RH, Hill AV (2003) Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Guerin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara. J Immunol 171: 1602–1609PubMedGoogle Scholar
  68. 68.
    McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K, Fletcher HA, Hill AV (2004) Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med 10: 1240–1244PubMedGoogle Scholar
  69. 69.
    Webster DP, Dunachie S, Vuola JM, Berthoud T, Keating S, Laidlaw SM, McConkey SJ, Poulton I, Andrews L, Andersen RF et al (2005) Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara. Proc Natl Acad Sci USA 102: 4836–4841PubMedGoogle Scholar
  70. 70.
    McConkey SJ, Reece WH, Moorthy VS, Webster D, Dunachie S, Butcher G, Vuola JM, Blanchard TJ, Gothard P, Watkins K et al (2003) Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans. Nat Med 9: 729–735PubMedGoogle Scholar
  71. 71.
    Dorrell L, Yang H, Ondondo B, Dong T, di Gleria K, Suttill A, Conlon C, Brown D, Williams P, Bowness P et al (2006) Expansion and diversification of virus-specific T cells following immunization of human immunodeficiency virus type 1 (HIV-1)-infected individuals with a recombinant modified vaccinia virus Ankara/HIV-1_gag vaccine. J Virol 80: 4705–4716PubMedGoogle Scholar
  72. 72.
    Tubiana R, Carcelain G, Vray M, Gourlain K, Dalban C, Chermak A, Rabian C, Vittecoq D, Simon A, Bouvet E et al (2005) Therapeutic immunization with a human immunodeficiency virus (HIV) type 1-recombinant canarypox vaccine in chronically HIV-infected patients: The Vacciter Study (ANRS 094). Vaccine 23: 4292–4301PubMedGoogle Scholar
  73. 73.
    Harrer E, Bauerle M, Ferstl B, Chaplin P, Petzold B, Mateo L, Handley A, Tzatzaris M, Vollmar J, Bergmann S et al (2005) Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load during treatment Interruption. Antivir Ther 10: 285–300PubMedGoogle Scholar
  74. 74.
    Cosma A, Nagaraj R, Buhler S, Hinkula J, Busch DH, Sutter G, Goebel FD, Erfle V (2003) Therapeutic vaccination with MVA-HIV-1_nef elicits Nef-specific T-helper cell responses in chronically HIV-1_infected individuals. Vaccine 22: 21–29PubMedGoogle Scholar
  75. 75.
    Taylor GS, Haigh TA, Gudgeon NH, Phelps RJ, Lee SP, Steven NM, Rickinson AB (2004) Dual stimulation of Epstein-Barr Virus (EBV)-specific CD4+-and CD8+-T-cell responses by a chimeric antigen construct: potential therapeutic vaccine for EBV-positive nasopharyngeal carcinoma. J Virol 78: 768–778PubMedGoogle Scholar
  76. 76.
    Garcia-Hernandez E, Gonzalez-Sanchez JL, Andrade-Manzano A, Contreras ML, Padilla S, Guzman CC, Jimenez R, Reyes L, Morosoli G, Verde ML, Rosales R (2006) Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine. Cancer Gene Ther 13: 592–597PubMedGoogle Scholar
  77. 77.
    Valdez Graham V, Sutter G, Jose MV, Garcia-Carranca A, Erfle V, Moreno Mendoza N, Merchant H, Rosales R (2000) Human tumor growth is inhibited by a vaccinia virus carrying the E2 gene of bovine papillomavirus. Cancer 88: 1650–1662PubMedGoogle Scholar
  78. 78.
    Corona Gutierrez CM, Tinoco A, Navarro T, Contreras ML, Cortes RR, Calzado P, Reyes L, Posternak R, Morosoli G, Verde ML, Rosales R (2004) Therapeutic vaccination with MVA E2_can eliminate precancerous lesions (CIN 1, CIN 2, and CIN 3) associated with infection by oncogenic human papillomavirus. Hum Gene Ther 15: 421–431PubMedGoogle Scholar
  79. 79.
    Adams M, Borysiewicz L, Fiander A, Man S, Jasani B, Navabi H, Evans AS, Mason M (2001) Clinical studies of human papilloma vaccines in cervical cancer. Adv Exp Med Biol 495: 419–427PubMedGoogle Scholar
  80. 80.
    Kaufmann AM, Stern PL, Rankin EM, Sommer H, Nuessler V, Schneider A, Adams M, Onon TS, Bauknecht T, Wagner U et al (2002) Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer. Clin Cancer Res 8: 3676–3685PubMedGoogle Scholar
  81. 81.
    Hodge JW, Poole DJ, Aarts WM, Gomez YA, Gritz L, Schlom J (2003) Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses. Cancer Res 63: 7942–7949PubMedGoogle Scholar
  82. 82.
    Marshall JL, Gulley JL, Arlen PM, Beetham PK, Tsang KY, Slack R, Hodge JW, Doren S, Grosenbach DW, Hwang J et al (2005) Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas. J Clin Oncol 23: 720–731PubMedGoogle Scholar
  83. 83.
    Eder JP, Kantoff PW, Roper K, Xu GX, Bubley GJ, Boyden J, Gritz L, Mazzara G, Oh WK, Arlen P et al (2000) A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer. Clin Cancer Res 6: 1632–1638PubMedGoogle Scholar
  84. 84.
    Smith CL, Dunbar PR, Mirza F, Palmowski MJ, Shepherd D, Gilbert SC, Coulie P, Schneider J, Hoffman E, Hawkins R et al (2005) Recombinant modified vaccinia Ankara primes functionally activated CTL specific for a melanoma tumor antigen epitope in melanoma patients with a high risk of disease recurrence. Int J Cancer 113: 259–266PubMedGoogle Scholar
  85. 85.
    van Baren N, Bonnet MC, Dreno B, Khammari A, Dorval T, Piperno-Neumann S, Lienard D, Speiser D, Marchand M, Brichard VG et al (2005) Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells. J Clin Oncol 23: 9008–9021PubMedGoogle Scholar
  86. 86.
    Kwak H, Horig H, Kaufman HL (2003) Poxviruses as vectors for cancer immunotherapy. Curr Opin Drug Discov Devel 6: 161–168PubMedGoogle Scholar
  87. 87.
    Liu M, Acres B, Balloul JM, Bizouarne N, Paul S, Slos P, Squiban P (2004) Gene-based vaccines and immunotherapeutics. Proc Natl Acad Sci USA 101Suppl 2: 14567–14571PubMedGoogle Scholar
  88. 88.
    Doehn C, Jocham D (2000) Technology evaluation: TG-1031, Transgene SA. Curr Opin Mol Ther 2: 106–111PubMedGoogle Scholar
  89. 89.
    Palena C, Foon KA, Panicali D, Yafal AG, Chinsangaram J, Hodge JW, Schlom J, Tsang KY (2005) Potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules. Blood 106: 3515–3523PubMedGoogle Scholar
  90. 90.
    Oertli D, Marti WR, Zajac P, Noppen C, Kocher T, Padovan E, Adamina M, Schumacher R, Harder F, Heberer M, Spagnoli GC (2002) Rapid induction of specific cytotoxic T lymphocytes against melanoma-associated antigens by a recombinant vaccinia virus vector expressing multiple immunodominant epitopes and costimulatory molecules in vivo. Hum Gene Ther 13: 569–575PubMedGoogle Scholar
  91. 91.
    Hodge JW, Abrams S, Schlom J, Kantor JA (1994) Induction of antitumor immunity by recombinant vaccinia viruses expressing B7-1 or B7-2 costimulatory molecules. Cancer Res 54: 5552–5555PubMedGoogle Scholar
  92. 92.
    Espenschied J, Lamont J, Longmate J, Pendas S, Wang Z, Diamond DJ, Ellenhorn JD (2003) CTLA-4_blockade enhances the therapeutic effect of an attenuated poxvirus vaccine targeting p53_in an established murine tumor model. J Immunol 170: 3401–3407PubMedGoogle Scholar
  93. 93.
    Drexler I, Antunes E, Schmitz M, Wolfel T, Huber C, Erfle V, Rieber P, Theobald M, Sutter G (1999) Modified vaccinia virus Ankara for delivery of human tyrosinase as melanoma-associated antigen: induction of tyrosinaseand melanoma-specific human leukocyte antigen A* 0201-restricted cytotoxic T cells in vitro and in vivo. Cancer Res 59: 4955–4963PubMedGoogle Scholar
  94. 94.
    Di Nicola M, Carlo-Stella C, Mortarini R, Baldassari P, Guidetti A, Gallino GF, Del Vecchio M, Ravagnani F, Magni M, Chaplin P et al (2004) Boosting T cell-mediated immunity to tyrosinase by vaccinia virus-transduced, CD34(+)-derived dendritic cell vaccination: a phase I trial in metastatic melanoma. Clin Cancer Res 10: 5381–5390PubMedGoogle Scholar
  95. 95.
    Parato KA, Senger D, Forsyth PA, Bell JC (2005) Recent progress in the battle between oncolytic viruses and tumours. Nat Rev Cancer 5: 965–976PubMedGoogle Scholar
  96. 96.
    Thorne SH, Hwang TH, Kirn DH (2005) Vaccinia virus and oncolytic virotherapy of cancer. Curr Opin Mol Ther 7: 359–365PubMedGoogle Scholar
  97. 97.
    McFadden G (2005) Poxvirus tropism. Nat Rev Microbiol 3: 201–213PubMedGoogle Scholar
  98. 98.
    Mastrangelo MJ, Maguire HC Jr, Eisenlohr LC, Laughlin CE, Monken CE, McCue PA, Kovatich AJ, Lattime EC (1999) Intratumoral recombinant GMCSF-encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Ther 6: 409–422PubMedGoogle Scholar
  99. 99.
    Zeh HJ, Bartlett DL (2002) Development of a replication-selective, oncolytic poxvirus for the treatment of human cancers. Cancer Gene Ther 9: 1001–1012PubMedGoogle Scholar
  100. 100.
    Buller RM, Smith GL, Cremer K, Notkins AL, Moss B (1985) Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype. Nature 317: 813–815PubMedGoogle Scholar
  101. 101.
    Buller RM, Chakrabarti S, Cooper JA, Twardzik DR, Moss B (1988) Deletion of the vaccinia virus growth factor gene reduces virus virulence. J Virol 62: 866–874PubMedGoogle Scholar
  102. 102.
    McCart JA, Ward JM, Lee J, Hu Y, Alexander HR, Libutti SK, Moss B, Bartlett DL (2001) Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res 61: 8751–8757PubMedGoogle Scholar
  103. 103.
    Guo ZS, Naik A, O’Malley ME, Popovic P, Demarco R, Hu Y, Yin X, Yang S, Zeh HJ, Moss B, Lotze MT, Bartlett DL (2005) The enhanced tumor selectivity of an oncolytic vaccinia lacking the host range and antiapoptosis genes SPI-1 and SPI-2. Cancer Res 65: 9991–9998PubMedGoogle Scholar
  104. 104.
    Wang F, Ma Y, Barrett JW, Gao X, Loh J, Barton E, Virgin HW, McFadden G (2004) Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier. Nat Immunol 5: 1266–1274PubMedGoogle Scholar
  105. 105.
    Lun X, Yang W, Alain T, Shi ZQ, Muzik H, Barrett JW, McFadden G, Bell J, Hamilton MG, Senger DL, Forsyth PA (2005) Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas. Cancer Res 65: 9982–9990PubMedGoogle Scholar
  106. 106.
    Staib C, Kisling S, Erfle V, Sutter G (2005) Inactivation of the viral interleukin 1beta receptor improves CD8+ T-cell memory responses elicited upon immunization with modified vaccinia virus Ankara. J Gen Virol 86: 1997–2006PubMedGoogle Scholar
  107. 107.
    Ishii KJ, Coban C, Kato H, Takahashi K, Torii Y, Takeshita F, Ludwig H, Sutter G, Suzuki K, Hemmi H et al (2006) A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Nat Immunol 7: 40–48PubMedGoogle Scholar
  108. 108.
    Clark RH, Kenyon JC, Bartlett NW, Tscharke DC, Smith GL (2006) Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy. J Gen Virol 87: 29–38PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2007

Authors and Affiliations

  • Barbara S. Schnierle
    • 1
  • Yasemin Suezer
    • 1
  • Gerd Sutter
    • 1
  1. 1.Department of VirologyPaul-Ehrlich-InstitutLangenGermany

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