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Assembly of trans-encapsidated recombinant viral vectors engineered from Tobacco mosaic virus and Semliki Forest virus and their evaluation as immunogens.
Smith, Mark L; Corbo, Tina; Bernales, Jacqueline; Lindbo, John A; Pogue, Gregory P; Palmer, Kenneth E; McCormick, Alison A.
Afiliação
  • Smith ML; Large Scale Biology Corporation, 3333 Vaca Valley Parkway, Suite 1000, Vacaville, CA 95688, USA.
Virology ; 358(2): 321-33, 2007 Feb 20.
Article em En | MEDLINE | ID: mdl-17014881
ABSTRACT
RNA virus vectors are attractive vaccine delivery agents capable of directing high-level gene expression without integration into host cell DNA. However, delivery of non-encapsidated RNA viral vectors into animal cells is relatively inefficient. By introducing the tobacco mosaic virus (TMV) origin of assembly into the RNA genome of Semliki Forest virus (SFV), we generated an SFV expression vector that could be efficiently packaged (trans-encapsidated) in vitro by purified TMV coat protein (CP). Using cellular assays, pseudovirus disassembly, RNA replication and reporter gene expression were demonstrated. We also evaluated the immune response to trans-encapsidated recombinant SFV carrying a model antigen gene (beta-galactosidase) in C57/B6 mice. Relative to RNA alone, vector encapsidation significantly improved the humoral and cellular immune responses. Furthermore, reassembly with recombinant TMV CPs permitted the display of peptide epitopes on the capsid surface as either genetic fusions or through chemical conjugation, to complement the immunoreactivity of the encapsidated RNA genetic payload. The SFV vector/TMV CP system described provides an alternative nucleic acid delivery mechanism that is safe, easy to manufacture in vitro and that also facilitates the generation of unique nucleic acid/protein antigen compositions.
Assuntos
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Base de dados: MEDLINE Assunto principal: Vírus da Floresta de Semliki / Vírus do Mosaico do Tabaco / Proteínas Virais / RNA Viral / Vacinas Virais / Beta-Galactosidase / Vetores Genéticos Limite: Animals Idioma: En Ano de publicação: 2007 Tipo de documento: Article
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Base de dados: MEDLINE Assunto principal: Vírus da Floresta de Semliki / Vírus do Mosaico do Tabaco / Proteínas Virais / RNA Viral / Vacinas Virais / Beta-Galactosidase / Vetores Genéticos Limite: Animals Idioma: En Ano de publicação: 2007 Tipo de documento: Article