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Hybrid Alphavirus-rhabdovirus Propagating Replicon Particles Are Versatile and Potent Vaccine Vectors

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Specialty Science
Date 2008 Apr 9
PMID 18391206
Citations 24
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Abstract

Self-propagating, infectious, virus-like particles are generated in animal cell lines transfected with a Semliki Forest virus RNA replicon encoding a single viral structural protein, the vesicular stomatitis virus (VSV) glycoprotein. We show here that these infectious particles, which we call propagating replicons, are potent inducers of neutralizing antibody in animals yet are nonpathogenic. Mice vaccinated with a single dose of the particles generated high titers of VSV-neutralizing antibody and were protected from a subsequent lethal challenge with VSV. Induction of antibody required RNA replication. We also report that additional genes (including an HIV-1 envelope protein gene) expressed from the propagating replicons induced strong cellular immune responses to the corresponding proteins after a single inoculation. Our studies reveal the potential of these particles as simple and safe vaccine vectors inducing strong humoral and cellular immune responses.

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References
1.
Masopust D, Vezys V, Marzo A, Lefrancois L . Preferential localization of effector memory cells in nonlymphoid tissue. Science. 2001; 291(5512):2413-7. DOI: 10.1126/science.1058867. View

2.
Shirai M, Pendleton C, Berzofsky J . Broad recognition of cytotoxic T cell epitopes from the HIV-1 envelope protein with multiple class I histocompatibility molecules. J Immunol. 1992; 148(6):1657-67. View

3.
Publicover J, Ramsburg E, Rose J . Characterization of nonpathogenic, live, viral vaccine vectors inducing potent cellular immune responses. J Virol. 2004; 78(17):9317-24. PMC: 506945. DOI: 10.1128/JVI.78.17.9317-9324.2004. View

4.
Salonen A, Ahola T, Kaariainen L . Viral RNA replication in association with cellular membranes. Curr Top Microbiol Immunol. 2004; 285:139-73. PMC: 7120253. DOI: 10.1007/3-540-26764-6_5. View

5.
Karlsson G, Liljestrom P . Delivery and expression of heterologous genes in mammalian cells using self-replicating alphavirus vectors. Methods Mol Biol. 2004; 246:543-57. DOI: 10.1385/1-59259-650-9:543. View