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Therapeutic and prophylactic applications of alphavirus vectors

Published online by Cambridge University Press:  11 November 2008

Gregory J. Atkins ,
Marina N. Fleeton  and
Brian J. Sheahan
Gregory J. Atkins*
Affiliation:
Virus Group, Department of Microbiology, School of Genetics and Microbiology, Trinity College, Dublin 2, Ireland.
Marina N. Fleeton
Affiliation:
Virus Group, Department of Microbiology, School of Genetics and Microbiology, Trinity College, Dublin 2, Ireland.
Brian J. Sheahan
Affiliation:
Veterinary Sciences Centre, UCD School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Dublin 4, Ireland.
*
*Corresponding author: Gregory J. Atkins, Virus Group, Department of Microbiology, School of Genetics and Microbiology, Trinity College, Dublin 2, Ireland. Tel: +353 1 8961415; Fax: +353 1 6799294; E-mail: [email protected]
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Abstract

Alphavirus vectors are high-level, transient expression vectors for therapeutic and prophylactic use. These positive-stranded RNA vectors, derived from Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus, multiply and are expressed in the cytoplasm of most vertebrate cells, including human cells. Part of the genome encoding the structural protein genes, which is amplified during a normal infection, is replaced by a transgene. Three types of vector have been developed: virus-like particles, layered DNA–RNA vectors and replication-competent vectors. Virus-like particles contain replicon RNA that is defective since it contains a cloned gene in place of the structural protein genes, and thus are able to undergo only one cycle of expression. They are produced by transfection of vector RNA, and helper RNAs encoding the structural proteins. Layered DNA–RNA vectors express the Semliki Forest virus replicon from a cDNA copy via a cytomegalovirus promoter. Replication-competent vectors contain a transgene in addition to the structural protein genes. Alphavirus vectors are used for three main applications: vaccine construction, therapy of central nervous system disease, and cancer therapy.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 10 , October 2008 , e33
Copyright
Copyright © Cambridge University Press 2008

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References

References

1Strauss, J.H. and Strauss, E.G. (1994) The alphaviruses: gene expression, replication and evolution. Microbiol Rev 58, 491-562CrossRefGoogle ScholarPubMed
2Liljestrom, P. and Garoff, H. (1991) A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology (N Y) 9, 1356-136CrossRefGoogle ScholarPubMed
3Smithburn, K.C. and Haddow, A.J. (1944) Semliki Forest virus. I. Isolation and pathogenic properties. J Immunol 49, 141-157CrossRefGoogle Scholar
4Mathiot, C.C. et al. (1990) An outbreak of human Semliki Forest virus infection in Central African Republic. Am J Trop Med Hyg 42, 386-393CrossRefGoogle Scholar
5Willems, W.R. et al. (1979) Semliki Forest virus: cause of a fatal case of human encephalitis. Science 203, 1127-1129CrossRefGoogle ScholarPubMed
6HHS Publication (1999) Biosafety in Microbiological and Biomedical Laboratories (4th edn), US Government Priniting Office, Washington, USAGoogle Scholar
7E.C. Council Directive 93/88/EEC (1993) The protection of workers from risks related to exposure to biological agents at work. Official Journal of the European Communities 268, 71-82Google Scholar
8Laine, M., Luukkainen, R. and Toivanen, A. (2004) Sindbis viruses and other alphaviruses as cause of human arthritic disease. J Intern Med 256, 457-471CrossRefGoogle ScholarPubMed
9Polo, J.M. et al. (1988) Molecular analysis of Sindbis virus pathogenesis in neonatal mice by using virus recombinants constructed in vitro. J Virol 62, 2124-2133CrossRefGoogle ScholarPubMed
10Pushko, P. et al. (1997) Replicon-helper systems from attenuated Venezuelan equine encephalitis virus: expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo. Virology 239, 389-401CrossRefGoogle ScholarPubMed
11Atkins, G.J., Sheahan, B.J. and Liljeström, P. (1999) The molecular pathogenesis of Semliki Forest virus: a model virus made useful? J Gen Virol 80, 2287-2297CrossRefGoogle Scholar
12Bradish, C.J., Allner, K. and Maber, H.B. (1972) Infection, interaction and the expression of virulence by defined strains of Semliki forest virus. J Gen Virol 16, 359-372CrossRefGoogle ScholarPubMed
13Smerdou, C. and Liljeström, P. (1999) Two-helper RNA system for production of recombinant Semliki forest virus particles. J Virol 73, 1092-1098CrossRefGoogle ScholarPubMed
14Berglund, P. et al. (1998) Enhancing immune responses using suicidal DNA vaccines. Nat Biotechnol 16, 562-565CrossRefGoogle ScholarPubMed
15Ljungberg, K. et al. (2007) Increased immunogenicity of a DNA-launched Venezuelan equine encephalitis virus-based replicon DNA vaccine. J Virol 81, 13412-13423CrossRefGoogle ScholarPubMed
16Tamang, D. et al. (2004) The use of a double subgenomic Sindbis virus expression system to study mosquito gene function: effects of antisense nucleotide number and duration of viral infection on gene silencing efficiency. Insect Mol Biol 13, 595-602CrossRefGoogle ScholarPubMed
17Galbraith, S.E., Sheahan, B.J. and Atkins, G.J. (2006) Deletions in the hypervariable domain of the nsP3 gene attenuate Semliki Forest virus virulence. J Gen Virol 87, 937-947CrossRefGoogle ScholarPubMed
18Casales, E. et al. (2008) Development of a new noncytopathic Semliki Forest virus vector providing high expression levels and stability. Virology 376, 242-251CrossRefGoogle ScholarPubMed
19Lundstrom, K. et al. (2003) Novel Semliki Forest virus vectors with reduced cytotoxicity and temperature sensitivity for long-term enhancement of transgene expression. Mol Ther 7, 202-209CrossRefGoogle ScholarPubMed
20Vähä-Koskela, M.J. et al. (2003) A novel neurotropic expression vector based on the avirulent A7(74) strain of Semliki Forest virus. J Neurovirol 9, 1-15CrossRefGoogle ScholarPubMed
21Vähä-Koskela, M.J., Heikkilä, J.E. and Hinkkanen, A.E. (2007) Oncolytic viruses in cancer therapy. Cancer Lett 254, 178-216CrossRefGoogle ScholarPubMed
22Morris-Downes, M.M. et al. (2001) Semliki Forest virus-based vaccines: persistence, distribution and pathological analysis in two animal systems. Vaccine 19, 1978-1988CrossRefGoogle ScholarPubMed
23Riezebos-Brilman, A. et al. (2007) A comparative study on the immunotherapeutic efficacy of recombinant Semliki Forest virus and adenovirus vector systems in a murine model for cervical cancer. Gene Ther 14, 1695-1704CrossRefGoogle Scholar
24Fleeton, M.N. et al. (2001) Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickborne encephalitis virus. J Infect Dis 183, 1395-1398CrossRefGoogle Scholar
25Riezebos-Brilman, A. et al. (2006) Recombinant alphaviruses as vectors for anti-tumour and anti-microbial immunotherapy. J Clin Virol 35, 233-243CrossRefGoogle ScholarPubMed
26Lundstrom, K. (2003) Alphavirus vectors for vaccine production and gene therapy. Expert Rev Vaccines 2, 447-459CrossRefGoogle ScholarPubMed
27Bredenbeek, P.J. et al. (1993) Sindbis virus expression vectors: packaging of RNA replicons by using defective helper RNAs. J Virol 67, 6439-6446CrossRefGoogle ScholarPubMed
28Perri, S. et al. (2003) An alphavirus replicon particle chimera derived from venezuelan equine encephalitis and sindbis viruses is a potent gene-based vaccine delivery vector. J Virol 77, 10394-10403CrossRefGoogle ScholarPubMed
29Vajdy, M. et al. (2001) Human immunodeficiency virus type 1 Gag-specific vaginal immunity and protection after local immunization with sindbis virus-based replicon particles. J Infect Dis 184, 1613-1616CrossRefGoogle ScholarPubMed
30Dong, M. et al. (2003) Induction of primary virus-cross-reactive human immunodeficiency virus type 1-neutralizing antibodies in small mammals by using an alphavirus-derived in vivo expression system. J Virol 77, 3119-3130CrossRefGoogle ScholarPubMed
31Hanke, T. et al. (2003) Construction and immunogenicity in a prime-boost regimen of a Semliki Forest virus-vectored experimental HIV clade A vaccine. J Gen Virol 84, 361-368CrossRefGoogle Scholar
32Sundback, M. et al. (2005) Efficient expansion of HIV-1-specific T cell responses by homologous immunization with recombinant Semliki Forest virus particles. Virology 341, 190-202CrossRefGoogle ScholarPubMed
33Forsell, M.N. et al. (2007) Increased human immunodeficiency virus type 1 Env expression and antibody induction using an enhanced alphavirus vector. J Gen Virol 88, 2774-2779CrossRefGoogle ScholarPubMed
34Forsell, M.N. et al. (2005) Biochemical and immunogenic characterization of soluble human immunodeficiency virus type 1 envelope glycoprotein trimers expressed by semliki forest virus. J Virol 79, 10902-10914CrossRefGoogle ScholarPubMed
35Davis, N.I. et al. (2000) Vaccination of macaques against pathogenic simian immunodeficiency virus with Venezuelan equine encephalitis virus replicon particles. J Virol 74, 371-378CrossRefGoogle ScholarPubMed
36Nilsson, C. et al. (2001) Enhanced simian immunodeficiency virus-specific immune responses in macaques induced by priming with recombinant Semliki forest virus and boosting with modified vaccinia virus Ankara. Vaccine 19, 3526-3536CrossRefGoogle ScholarPubMed
37Johnston, R.E. et al. (2005) Vaccination of macaques with SIV immunogens delivered by Venezuelan equine encephalitis virus replicon particle vectors followed by a mucosal challenge with SIVsmE660. Vaccine 23, 4969-4979CrossRefGoogle ScholarPubMed
38Xu, R. et al. (2006) Characterization of immune responses elicited in macaques immunized sequentially with chimeric VEE/SIN alphavirus replicon particles expressing SIV Gag and/or HIVEnv and with recombinant HIVgp140Env protein. AIDS Res Hum Retroviruses 22, 1022-1030CrossRefGoogle ScholarPubMed
39Ehrengruber, M.U. et al. (2003) Semliki Forest virus A7(74) transduces hippocampal neurons and glial cells in a temperature-dependent dual manner. J Neurovirol 9, 16-28CrossRefGoogle Scholar
40Graham, A. et al. (2006) CNS gene therapy applications of the Semliki Forest virus vector are limited by neurotoxicity. Mol Ther 13, 631-635CrossRefGoogle ScholarPubMed
41Sammin, D.J. et al. (1999) Cell death mechanisms in the olfactory bulb of rats infected intranasally with Semliki forest virus. Neuropathol Appl Neurobiol 25, 236-243CrossRefGoogle ScholarPubMed
42Jerusalmi, A. et al. (2003) Effect of intranasal administration of Semliki Forest virus recombinant particles expressing reporter and cytokine genes on the progression of experimental autoimmune encephalomyelitis. Mol Ther 8, 886-894CrossRefGoogle ScholarPubMed
43Quinn, K. et al. (2008) Effect of intranasal administration of Semliki Forest virus recombinant particles expressing interferon-β on the progression of experimental autoimmune encephalomyelitis. Mol Med Rep 1, 335-342Google ScholarPubMed
44Vähä-Koskela, M.J. et al. (2007) Semliki Forest virus vectors expressing transforming growth factor beta inhibit experimental autoimmune encephalomyelitis in Balb/c mice. Biochem Biophys Res Commun 355, 776-781CrossRefGoogle ScholarPubMed
45Nygårdas, P.T. et al. (2004) Treatment of experimental autoimmune encephalomyelitis with a neurotropic alphavirus vector expressing tissue inhibitor of metalloproteinase-2. Scand J Immunol 60, 372-381CrossRefGoogle ScholarPubMed
46Kelly, B.J., Fleeton, M.N. and Atkins, G.J. (2007) Potential of alphavirus vectors in the treatment of advanced solid tumors. Recent Patents Anticancer Drug Discov 2, 159-166CrossRefGoogle ScholarPubMed
47Atkins, G.J. et al. (2004) Alphaviruses and their derived vectors as anti-tumor agents. Curr Cancer Drug Targets 4, 597-607CrossRefGoogle ScholarPubMed
48Yamanaka, R. (2004) Alphavirus vectors for cancer gene therapy. Int J Oncol 24, 919-923Google ScholarPubMed
49Lundstrom, K. (2002) Alphavirus vectors as tools in cancer gene therapy. Technol Cancer Res Treat 1, 83-88CrossRefGoogle ScholarPubMed
50Velders, M.P. et al. (2001) Eradication of established tumors by vaccination with Venezuelan equine encephalitis virus replicon particles delivering human papillomavirus 16 E7 RNA. Cancer Res 61, 7861-7867Google ScholarPubMed
51Daemen, T. et al. (2003) Eradication of established HPV16-transformed tumours after immunisation with recombinant Semliki Forest virus expressing a fusion protein of E6 and E7. Vaccine 21, 1082-1088CrossRefGoogle ScholarPubMed
52Cheng, W.F. et al. (2006) Sindbis virus replicon particles encoding calreticulin linked to a tumor antigen generate long-term tumor-specific immunity. Cancer Gene Ther 13, 873-885CrossRefGoogle ScholarPubMed
53Cassetti, M.C. et al. (2004) Antitumor efficacy of Venezuelan equine encephalitis virus replicon particles encoding mutated HPV16 E6 and E7 genes. Vaccine 22, 520-527CrossRefGoogle ScholarPubMed
54Riezebos-Brilman, A. et al. (2005) Induction of human papillomavirus E6/E7-specific cytotoxic T-lymphocyte activity in immune-tolerant, E6/E7 transgenic mice. Gene Ther 12, 1410-1414CrossRefGoogle ScholarPubMed
55Laust, A.K. et al. (2007) VlP immunotherapy targeting neu: treatment efficacy and evidence for immunoediting in a stringent rat mammary tumour model. Breast Cancer Res Treat 106, 371-382CrossRefGoogle Scholar
56Wang, X. et al. (2005) Alphavirus replicon particles containing the gene for HER2/neu inhibit breast cancer growth and tumorigenesis. Breast Cancer Res 7, 145-155CrossRefGoogle ScholarPubMed
57Leslie, M.C. et al. (2007) Immunization against MUC18/MCAM, a novel antigen that drives melanoma invasion and metastsis. Gene Ther 14, 316-323CrossRefGoogle Scholar
58Vähä-Koskela, M.J. et al. (2006) Oncolytic capacity of attenuated replicative semliki forest virus in human melanoma xenografts in severe combined immunodeficient mice. Cancer Res 66, 7185-7194CrossRefGoogle ScholarPubMed
59Wollmann, G., Tattersall, P. and van den Pol, A.N. (2005) Targeting human glioblastoma cells: comparison of nine viruses with oncolytic potential. J Virol 79, 6005-6022CrossRefGoogle ScholarPubMed
60Zhang, J., Frolov, I. and Russell, S.J. (2004) Gene therapy for malignant glioma using Sindbis vectors expressinga fusogenic membrane glycoprotein. J Gene Med 6, 1082-1091CrossRefGoogle Scholar
61Lee, J.S. et al. (2006) Growth inhibitory effect of triple anti-tumor gene transfer using Semliki Forest virus vector in glioblastoma cells. Int J Oncol 28, 649-654Google ScholarPubMed
62Maatta, A.M. et al. (2007) Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models. Int J Cancer 121, 863-870CrossRefGoogle ScholarPubMed
63Garcia-Hernandez Mde, L. et al. (2007) In vivo effects of vaccination with six-transmembrane epithelial antigen of the prostate: a candidate antigen for treating prostate cancer. Cancer Res 67, 1344-1351CrossRefGoogle ScholarPubMed
64Garcia-Hernandez, M. de la L. et al. (2008) Prostate stem cell antigen vaccination induces a long-term protective immune response against prostate cancer in the absence of autoimmunity. Cancer Res 68, 861-869CrossRefGoogle ScholarPubMed
65Durso, R.J. et al. (2007) A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses. Clin Cancer Res 13, 3999-4008CrossRefGoogle ScholarPubMed
66Tseng, J.C. et al. (2007) Restricted tissue tropism and acquired resistance to Sindbis viral vector expression in the absence of innate and adaptive immunity. Gene Ther 14, 1166-1174CrossRefGoogle ScholarPubMed
67Hurtado, A. et al. (2005) Identification of amino acids of Sindbis virus E2 protein involved in targeting tumor metastases in vivo. Mol Ther 12, 813-823CrossRefGoogle ScholarPubMed
68Tseng, J.C. et al. Using sindbis viral vectors for specific detection and suppression of advanced ovarian cancer in animal models. Cancer Res 64, 6684-6692CrossRefGoogle Scholar
69Tseng, J.C. et al. (2004) Systemic tumor targeting and killing by Sindbis viral vectors. Nat Biotechnol 22, 70-77CrossRefGoogle ScholarPubMed
70Rodriguez-Madoz, J.R., Ptrieto, J. and Smerdou, C. (2007) Biodistribution and tumor infectivity of semliki forest virus vectors in mice: effects of readministration. Mol Ther 15, 2164-2171CrossRefGoogle ScholarPubMed
71Murphy, A.M. et al. (2000) Inhibition of human lung carcinoma cell growth by apoptosis induction using Semliki Forest virus recombinant particles. Gene Ther 17, 1477-1482CrossRefGoogle Scholar
72Murphy, A.M, Sheahan, B.J. and Atkins, G.J. (2001) Induction of apoptosis in BCL-2-expressing rat prostate cancer cells using the Semliki Forest virus vector. Int J Cancer 94, 572-578CrossRefGoogle ScholarPubMed
73Smyth, J.W. et al. (2005) Treatment of rapidly growing K-BALB and CT26 mouse tumours using Semliki Forest virus and its derived vector. Gene Ther 12, 147-159CrossRefGoogle ScholarPubMed
74Chikkanna-Gowda, C.P. et al. (2006) Inhibition of murine K-BALB and CT26 tumour growth using a Semliki Forest virus vector with enhanced expression of IL-18. Oncol Rep 16, 713-719Google ScholarPubMed
75Chikkanna-Gowda, C.P. et al. (2005) Regression of mouse tumours and inhibition of metastases following administration of a Semliki Forest virus vector with enhanced expression of IL-12. Gene Ther 12, 1253-1263CrossRefGoogle ScholarPubMed
76Rodriguez-Madoz, J.R., Prieto, J. and Smerdou, C. (2005) Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas. Mol Ther 12, 153-163CrossRefGoogle ScholarPubMed
77Lyons, J.A. (2007) Inhibition of angiogenesis by a Semliki Forest virus vector expressing VEGFR-2 reduces tumour growth and metastasis in mice. Gene Ther 14, 503-513CrossRefGoogle ScholarPubMed
78Hubby, B. et al. (2007) Development and preclinical evaluation of an alphavirus replicon vaccine for influenza. Vaccine 25, 8180-8189CrossRefGoogle ScholarPubMed
79Villa, I.I. et al. (2006) High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer 95, 1459-1466CrossRefGoogle ScholarPubMed
80Kistner, O. et al. (2007) The preclinical testing of a formaldehyde inactivated Ross River virus vaccine designed for use in humans. Vaccine 25, 4845-4852CrossRefGoogle ScholarPubMed
81Ren, H. et al. (2003) Immunogene therapy of recurrent glioblastoma multiforme with a liposomally encapsulated replication-incompetent Semliki forest virus vector carrying the human interleukin-12 gene-a phase I/II clinical protocol. J Neurooncol 64, 147-254CrossRefGoogle ScholarPubMed
82Pugachev, K.V. et al. (1995) Double-subgenomic Sindbis virus recombinants expressing immunogenic proteins of Japanese encephalitis virus induce significant protection in mice against lethal JEV infection. Virology 212, 587-594CrossRefGoogle ScholarPubMed
83Seo, S.H. et al. (1977) The carboxyl-terminal 120-residue polypeptide of infectious bronchitis virus nucleocapsid induces cytotoxic T lymphocytes and protects chickens from acute infection. J Virol 71, 7889-7894CrossRefGoogle Scholar
84Hariharan, M.J. et al. (1998) DNA immunization against herpes simplex virus: enhanced efficacy using a Sindbis virus-based vector. J Virol 72, 950-958CrossRefGoogle ScholarPubMed
85Reddy, J.R. et al. (1999) Semliki forest virus vector carrying the bovine viral diarrhea virus NS3 (p80) cDNA induced immune responses in mice and expressed BVDV protein in mammalian cells. Comp Immunol Microbiol Infect Dis 22, 231-246CrossRefGoogle ScholarPubMed
86Morris-Downes, M.M. et al. (2001) A recombinant Semliki Forest virus particle vaccine encoding the prME and NS1 proteins of louping ill virus is effective in a sheep challenge model. Vaccine 19, 3877-3884CrossRefGoogle Scholar
87Fleeton, M.N. et al. (2000) Recombinant Semliki Forest virus particles expressing louping ill virus antigens induce a better protective response than plasmid-based DNA vaccines or an inactivated whole particle vaccine. J Gen Virol 81, 749-758CrossRefGoogle ScholarPubMed
88Fleeton, M.N. et al. (1999) Recombinant Semliki Forest virus particles encoding the prME or NS1 proteins of louping ill virus protect mice from lethal challenge. J Gen Virol 80, 1189-1198CrossRefGoogle ScholarPubMed
89Berglund, P. et al. (1999) Immunization with recombinant Semliki Forest virus induces protection against influenza challenge in mice. Vaccine 17, 497-507CrossRefGoogle ScholarPubMed
90Schultz-Cherry, S. et al. (2000) Influenza virus (A/HK/156/97) hemagglutinin expressed by an alphavirus replicon system protects chickens against lethal infection with Hong Kong-origin H5N1 viruses. Virology 278, 55-59CrossRefGoogle Scholar
91Tsuji, M. et al. (1998) Recombinant Sindbis viruses expressing a cytotoxic T-lymphocyte epitope of a malaria parasite or of influenza virus elicit protection against the corresponding pathogen in mice. J Virol 72, 6907-6910CrossRefGoogle ScholarPubMed
92Hevey, M. et al. (1998) Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates. Virology 251, 28-37CrossRefGoogle ScholarPubMed
93Colombage, G. et al. (1998) DNA-based and alphavirus-vectored immunisation with prM and E proteins elicits long-lived and protective immunity against the flavivirus, Murray Valley encephalitis virus. Virology 250, 151-163CrossRefGoogle Scholar
94Kamrud, K.I. et al. (1999) Comparison of the protective efficacy of naked DNA, DNA-based Sindbis replicon, and packaged Sindbis replicon vectors expressing Hantavirus structural genes in hamsters. Virology 266, 209-219CrossRefGoogle Scholar
95Pushko, P. et al. (2000) Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic fever virus. Vaccine 19, 142-153CrossRefGoogle ScholarPubMed
96Pushko, P. et al. (2001) Individual and bivalent vaccines based on alphavirus replicons protect guinea pigs against infection with Lassa and Ebola viruses. J Virol 75, 11677-11685CrossRefGoogle ScholarPubMed
97Balasuriya, U.B. et al. (2002) Alphavirus replicon particles expressing the two major envelope proteins of equine arteritis virus induce high level protection against challenge with virulent virus in vaccinated horses. Vaccine 20, 1609-1617CrossRefGoogle ScholarPubMed
98Balasuriya, U.B. et al. (2000) Expression of the two major envelope proteins of equine arteritis virus as a heterodimer is necessary for induction of neutralizing antibodies in mice immunized with recombinant Venezuelan equine encephalitis virus replicon particles. J Virol 74, 10623-10630CrossRefGoogle ScholarPubMed
99Chen, M. et al. (2002) Vaccination with recombinant alphavirus or immune-stimulating complex antigen against respiratory syncytial virus. J Immunol 169, 3208-3216CrossRefGoogle ScholarPubMed
100Elliott, M.B. et al. (2007) Alphavirus replicon particles encoding the fusion or attachment glycoproteins of respiratory syncytial virus elicit protective immune responses in BALB/c mice and functional serum antibodies in rhesus macaques. Vaccine 25, 7132-7144CrossRefGoogle ScholarPubMed
101Harrington, P.R. et al. (2002) Systemic, mucosal, and heterotypic immune induction in mice inoculated with Venezuelan equine encephalitis replicons expressing Norwalk virus-like particles. J Virol 76, 730-742CrossRefGoogle ScholarPubMed
102Burkhard, M.J. et al. (2002) Evaluation of FIV protein-expressing VEE-replicon vaccine vectors in cats. Vaccine 21, 258-268CrossRefGoogle ScholarPubMed
103Dory, D. et al. (2006) Prime-boost immunization using DNA vaccine and recombinant Orf virus protects pigs against Pseudorabies virus. Vaccine 24, 6256-6263CrossRefGoogle ScholarPubMed
104Li, N. et al. (2007) A Semliki Forest virus replicon vectored DNA vaccine expressing the E2 glycoprotein of classical swine fever virus protects pigs from lethal challenge. Vaccine 25, 2907-2912CrossRefGoogle ScholarPubMed
105Thornburg, N.J. et al. (2007) Vaccination with Venezuelan equine encephalitis replicons encoding cowpox virus structural proteins protects mice from intranasal cowpox virus challenge. Virology 362, 441-452CrossRefGoogle ScholarPubMed
106Reap, E.A. et al. (2007) Cellular and humoral immune responses to alphavirus replicon vaccines expressing cytomegalovirus pp65, IE1, and gB proteins. Clin Vaccine Immunol 14, 748-755CrossRefGoogle ScholarPubMed
107Callagy, S.J. et al. (2007) Semliki Forest virus vectors expressing the H and HN genes of measles and mumps viruses reduce immunity induced by the envelope protein genes of rubella virus. Vaccine 25, 7481-7490CrossRefGoogle Scholar
108Pan, C.H. et al. (2005) Modulation of disease, T cell responses, and measles virus clearance in monkeys vaccinated with H-encoding alphavirus replicon particles. Proc Natl Acad Sci U S A 102, 11581-11588CrossRefGoogle ScholarPubMed
109Pasetti, M.F. et al. (2007) Heterologous prime-boost strategy to immunize very young infants against measles: pre-clinical studies in rhesus macaques. Clin Pharmacol Ther 82, 672-685CrossRefGoogle ScholarPubMed
110Lee, J.S. et al. (2002) Immune protection against staphylococcal enterotoxin-induced toxic shock by vaccination with a Venezuelan equine encephalitis virus replicon. J Infect Dis 185, 1192-1196CrossRefGoogle ScholarPubMed
111Lee, J.S. et al. (2006) Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice. Vaccine 24, 6886-6892CrossRefGoogle ScholarPubMed
112Oñate, A.A. et al. (2005) An RNA vaccine based on recombinant Semliki Forest virus particles expressing the Cu,Zn superoxide dismutase protein of Brucella abortus induces protective immunity in BALB/c mice. Infect Immun 73, 3294-3300CrossRefGoogle ScholarPubMed
113Derrick, S.C., Yang, A.L. and Morris, S.L. (2005) Vaccination with a Sindbis virus-based DNA vaccine expressing antigen 85B induces protective immunity against Mycobacterium tuberculosis. Infect Immun 73, 7727-7735CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

Lui, T.C. and Kirn, D. (2008) Gene therapy progress and prospects cancer: oncolytic viruses. Gene Therapy 15, 877-884Google Scholar
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