Abstract
Due to their natural host-range restriction to avian species, canarypox virus (CP) and fowlpox virus (FP) represent efficient and safe vaccine vectors, as they correctly express transgenes in human cells, elicit complete immune responses, and show protective efficacy in preclinical animal models. At present, no information is available on the differences in the abortive replication of these two avipox viruses in mammalian cells. In the present study, the replicative cycles of CP and FP, wild-type and recombinants, are compared in permissive and non-permissive cells, using transmission electron microscopy. We demonstrate that in non-permissive cells, the replicative cycle is more advanced in FP than in CP, that human cells, whether immune or not, are less permissive to avipox replication than monkey cells, and that the presence of virus-like particles only occurs after FP infection. Overall, these data suggest that the use of FP recombinants is more appropriate than the use of CP for eliciting an immune response.
Similar content being viewed by others
Abbreviations
- CP:
-
Canarypox virus(es)
- FP:
-
Fowlpox virus(es)
- CPwt:
-
Canarypox wild-type
- FPwt:
-
Fowlpox wild-type
- CPgp :
-
CPgag/pol recombinant
- CPenv :
-
CPenv recombinant
- CPgpe :
-
CPgag/pol/env recombinant
- FPgp :
-
FPgag/pol recombinant
- FPenv :
-
FPenv recombinant
- HIV:
-
Human immunodeficiency virus
- SIV:
-
Simian immunodeficiency virus
- MVA:
-
Modified vaccinia virus Ankara
- NYVAC:
-
New York vaccine
- V:
-
Viroplasm
- VF:
-
Viral factories
- C:
-
Crescent(s)
- PS:
-
Paracrystalline structure(s)
- IV:
-
Immature virion(s)
- MV:
-
Mature virion(s)
- EV:
-
Extracellular virion(s)
- VLP:
-
Virus-like particle(s)
- CEF:
-
Chick embryo fibroblast(s)
- PBMC:
-
Peripheral blood mononuclear cell(s)
- MΦ:
-
Macrophage(s)
- DC:
-
Dendritic cell(s)
- TEM:
-
Transmission electron microscopy
References
Afonso C, Tulman ER, Lu Z, Zsak L, Kutish GF, Rock DL (2000) The genome of fowlpox virus. J Virol 74:3815–3831
Baxby D, Paoletti E (1992) Potential use of nonreplicating vectors as recombinant vaccines. Vaccine 10:8–9
Belshe RB, Stevens C, Gorse GJ, Buchbinder SP, Weinhold K, Sheppard H, Stablein D, Self SG, McNamara J, Frey SE, Flores J, Excler JL, Klein M, Habib RE, Duliege AM, Harro CD, Corey L, Keefer MC, Mulligan MJ, Wright PF, Celum C, Judson F, Mayer K, McKirnan D, Marmor M, Woody G (2001) Safety and immunogenicity of a canarypox-vectored human immunodeficiency virus Type 1 vaccine with or without gp120: a phase 2 study in higher- and lower-risk volunteers. J Infect Dis 183:1343–1352
Blanchard TJ, Alcami A, Andrea P, Smith GL (1998) Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine. J Gen Virol 79:1159–1167
Cao H, Kaleebu P, Hom D, Flores J, Agrawal D, Jones N, Serwanga J, Okello M, Walker C, Sheppard H, El-Habib R, Klein M, Mbidde E, Mugyenyi P, Walker B, Ellner J, Mugerwa R (2003) Immunogenicity of a recombinant human immunodeficiency virus (HIV)-canarypox vaccine in HIV-seronegative Ugandan volunteers: results of the HIV Network for prevention trials 007 vaccine study. J Infect Dis 187:887–895
Corey L, Mulligan M, Goepfert P, Sabbaj S, Clements-Mann ML, Harrow C, Schwartz D, Dolin R, Evans T, Keefer MC, Belshe R, Gorse GJ, Frey SE, McElrath MJ, Graham BS, Wright PF, Spearman P, Weinhold K, Montefiori D, Greenberg M, Klein M, El Habib R, Excler JL, Duliege A-M, Stablein D, Wolff M, Smith C, Grabowsky M, Savarese B, Clare Walker M (2001) Cellular and humoral immune responses to a canarypox vaccine containing human immunodeficiency virus Type 1 Env, Gag, and Pro in combination with RGP120 the AIDS vaccine evaluation group 022 protocol team. J Infect Dis 183:563–570
Coupar BEH, Purcell DFJ, Thomson SA, Ramshaw IA, Kent SJ, Boyle DB (2006) Fowlpox virus vaccines for HIV and SHIV clinical and pre-clinical trials. Vaccine 24:1378–1388
de Bruyn G, Rossini AJ, Chiu YL, Holman D, Elizaga ML, Frey SE, Burke DS, Evans TG, Corey L, Keefer MC (2004) Safety profile of recombinant canarypox HIV vaccines. Vaccine 22:704–713
Earl PL, Wyatt LS, Montefiori DC, Bilska M, Woodward R, Markham PD, Malley JD, Vogel TU, Allen TM, Watkins DI, Miller N, Moss B (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 294:270–281
Fang ZY, Kuli-Zade I, Spearman P (1999) Efficient human immunodeficiency virus (HIV)-1 Gag-Env pseudovirion formation elicited from mammalian cells by a canarypox HIV vaccine candidate. J Infect Dis 180:1122–1132
Franchini G, Gurunathan S, Baglyos L, Plotkin S, Tartaglia J (2004) Poxvirus-based vaccine candidates for HIV: two decades of experience with special emphasis on canarypox vectors. Expert Rev Vaccin 3:S75–S88
Fries LF, Tartaglia J, Taylor J, Kauffman EK, Meignier B, Paoletti E, Plotkin S (1996) Human safety and immunogenicity of a canarypox-rabies glycoprotein recombinant vaccine: an alternative poxvirus vector system. Vaccine 14:1171–1179
Goepfert PA, Horton H, McElrath MJ, Gurunathan S, Ferrari G, Tomaras GD, Montefiori DC, Allen M, Chiu YL, Spearman P, Fuchs JD, Koblin BA, Blattner WA, Frey SE, Keefer MC, Baden LR, Corey L (2005) High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects. J Infect Dis 192:1249–1259
Griffiths G, Roos N, Schleich S, Locker JK (2001) Structure and assembly of intracellular mature vaccinia virus: thin-section analyses. J Virol 75:11056–11070
Gupta K, Hudgens M, Corey L, McElrath MJ, Weinhold K, Montefiori DC, Gorse GJ, Frey SE, Keefer MC, Evans TG, Dolin R, Schwartz D, Harro CD, Graham BS, Spearman PW, Mulligan M, Goepfert P (2002) Safety and immunogenicity of a high-titered canarypox vaccine in combination with rgp120 in a diverse population of HIV-1-uninfected adults: AIDS vaccine evaluation group protocol 022A. J Acquir Immune Defic Syndr 29:254–261
Husain M, Weiberg AS, Moss B (2006) Existence of an operative pathway from the endoplasmic reticulum to the immature poxvirus membrane. Proc Natl Acad Sci USA 103:19506–19511
Irvine KR, Chamberlain RS, Shulman EP, Rosenberg SA, Restifo NP (1997) Enhancing efficacy of recombinant anticancer vaccines with prime/boost regimens that use two different vectors. J Natl Cancer Inst 89:1595–1601
Jenkins S, Gritz L, Fedor CH, O’Neill E, Cohen LK, Panicali DL (1991) Formation of lentivirus particles by mammalian cells infected with recombinant fowlpox virus. AIDS Res Hum Retrovir 7:991–997
Kent SJ, Zhao A, Dale CJ, Land S, Boyle DB, Ramshaw IA (2000) A recombinant avipoxvirus HIV-1 vaccine expressing interferon-gamma is safe and immunogenic in macaques. Vaccine 18:2250–2256
Kresge KJ (2009) Raft of results energizes researchers. IAVI Rep 13:4–17
Kyriakis CS, De Vleeschauwer A, Barb F, Bublot M, Van Reeth K (2009) Safety, immunogenicity and efficacy of poxvirus-based vector vaccines expressing the haemagglutinin gene of a highly pathogenic H5N1 avian influenza virus in pigs. Vaccine 27:2258–2264
Mayr A, Hochstein-Mintzel V, Stickl H (1975) Passage history, properties, and applicability of the attenuated vaccinia virus strain MVA. Infection 3:6–14
Nacsa J, Radaelli A, Edghill-Smith Y, Venzon D, Tsai WP, De Giuli Morghen C, Panicali DL, Tartaglia J, Franchini G (2004) Avipox-based simian immunodeficiency virus (SIV) vaccines elicit a high frequency of SIV-specific CD4+ and CD8+ T-cell responses in vaccinia-experienced SIVmac251-infected macaques. Vaccine 22:597–606
Perkus M, Limbach K, Paoletti E (1989) Cloning and expression of foreign genes in vaccinia virus, using a host range selection system. J Virol 63:3829–3836
Picard O, Lebas J, Imbert JC, Bigel P, Zagury D (1991) Complication of intramuscular/subcutaneous immune therapy in severely immune-compromised individuals. J Acquir Immune Defic Syndr 4:641–643
Radaelli A, Bonduelle O, Beggio P, Mahe B, Pozzi E, Elli V, Paganini M, Zanotto C, De Giuli Morghen C, Combadière B (2007) Prime-boost immunization with DNA, recombinant fowlpox virus and VLP(SHIV) elicit both neutralizing antibodies and IFNgamma-producing T cells against the HIV-envelope protein in mice that control env-bearing tumour cells. Vaccine 25:2128–2138
Radaelli A, De Giuli Morghen C (1994) Expression of HIV-1 envelope gene by recombinant avipoxvirus. Vaccine 12:1101–1109
Radaelli A, Gimelli M, Cremonesi C, Scarpini C, De Giuli Morghen C (1994) Humoral and cell mediated immunity in rabbits immunized with live non replicating avipox recombinants expressing the HIV-1sf2 env gene. Vaccine 12:1110–1117
Radaelli A, Zanotto C, Perletti G, Elli V, Vicenzi E, Poli G, De Giuli Morghen C (2003) Comparative analysis of immune responses and cytokine profiles elicited in rabbits by the combined use of recombinant fowlpox viruses, plasmid and virus-like particles in prime-boost vaccination protocols against SHIV. Vaccine 21:2052–2064
Rodriguez JR, Risco C, Carrascosa JL, Esteban M, Rodriguez D (1998) Vaccinia virus 15-kilodalton (A14L) protein is essential for assembly and attachment of viral crescents to virosomes. J Virol 72:1287–1296
Sabbaj S, Mulligan MJ, Hsieh R-H, McGhee JR (2000) Cytokine profiles in seronegative volunteers immunized with a recombinant canarypox and gp120 prime-boost HIV-1 vaccine. J Virol 14:1365–1374
Sadavis EC, Chang PW, Gulka G (1985) Morphogenesis of canary poxvirus and its entrance into inclusion bodies. Am J Vet Res 46:529–535
Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179:1109–1118
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 Vaccin 4:63–76
Sodeik B, Doms RW, Ericsson M, Hiller G, Machamer CE, van’t Hof W, van Meer G, Moss B, Griffiths G (1993) Assembly of vaccinia virus: role of the intermediate compartment between the endoplasmic reticulum and the Golgi stacks. J Cell Biol 121:521–541
Somogyi P, Frazier J, Skinner MA (1993) Fowlpox virus host range restriction: gene expression, DNA replication, and morphogenesis in nonpermissive mammalian cells. Virology 197:439–444
Tartaglia J, Perkus M, Taylor J, Norton EK, Audonnet JC, Cox WI, Davis D, van der Hoeven J, Meigneier B, Riviere M (1992) NYVAC: a highly attenuated strain of vaccinia virus. Virology 188:217–232
Tartaglia J, Taylor J, Cox WJ, Audonnet JC, Perkus M, Paoletti E, Radaelli A, De Giuli Morghen C, Meigneier B, Riviere M, Weinhold K (1993) Novel poxvirus strains as research tools and vaccine vectors. In: Koff WC, Wong-Staal F, Kennedy RC (eds) AIDS research reviews. Marcel Dekker, New York, pp 361–378
Taylor J, Paoletti E (1988) Fowlpox virus as a vector in non-avian species. Vaccine 6:466–468
Taylor J, Weinberg R, Kawaoka Y, Webster RG, Paoletti E (1988) Protective immunity against avian influenza induced by a fowlpox virus recombinant. Vaccine 6:504–508
Taylor J, Weinberg R, Languet B, Desmettre P, Paoletti E (1988) Recombinant fowlpox virus inducing protective immunity in nonavian species. Vaccine 6:497–503
Tulman ER, Alfonso CL, Lu Z, Zsak L, Kutish GF, Rock DL (2004) The genome of canarypox virus. J Virol 78:353–366
Wolffe EJ, Moore DM, Peters PJ, Moss B (1996) Vaccinia virus A17L open reading frame encodes an essential component of nascent viral membranes that is required to initiate morphogenesis. J Virol 70:2797–2808
Xia J, Ramanathan B, Barsoum J, Deschenes GR, Ba L, Binley J, Schiller D, Bauer DE, Chen DC, Hurley A, Gebuhrer L, El Habib R, Caudrelier P, Klein M, Zhang L, Ho DD, Markowitz M (2002) Safety and immunogenicity of ALVAC vCP1452 and recombinant gp160 in newly human immunodeficiency virus Type 1-infected patients treated with prolonged highly active antiretroviral therapy. J Virol 76:2206–2216
Zanotto C, Paganini M, Elli V, Basavecchia V, Neri M, De Giuli Morghen C, Radaelli A (2005) Molecular and biological characterization of simian-human immunodeficiency virus-like particles produced by recombinant fowlpox viruses. Vaccine 23:4745–4753
Acknowledgments
This project was supported in part by the Italian Ministry of Health (National Programme of AIDS, grant nos. 45F.10, 45G.10, 30G.26 and 45D/1.20), by the Italian Ministry of University and Research (Cofin-PRIN 2007) and by the EC Microbicide Program “SHIVA” no. 503162. We also thank Dr. Christopher Berrie for editorial assistance with the manuscript.
Conflict of interest statement
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
S. Pacchioni and L. Volonté contributed equally to this work.
Rights and permissions
About this article
Cite this article
Pacchioni, S., Volonté, L., Zanotto, C. et al. Canarypox and fowlpox viruses as recombinant vaccine vectors: an ultrastructural comparative analysis. Arch Virol 155, 915–924 (2010). https://doi.org/10.1007/s00705-010-0663-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00705-010-0663-7