title: HSV-1 amplicon vectors that direct the in situ production of foot-and-mouth disease virus antigens in mammalian cells can be used for genetic immunization.
abstract: HSV-1 amplicon vectors encoding heterologous antigens were capable to mediate in situ generation of protein synthesis and to generate a specific immune response to the corresponding antigens. In this study, foot-and-mouth disease (FMD) virus antigens were used to generate a genetic vaccine prototype. The amplicons were designed to provide a high safety profile as they do not express any HSV-1 genes when packaged using a helper virus-free system, and they are able to encapsidate several copies of the transgene or allow the simultaneous expression of different genes. Virus-like particles were produced after cell processing of the delivered DNA. Inoculation of mice with 5 × 10(5) transducing units of amplicon vectors resulted in FMDV-specific humoral responses in the absence of adjuvants, which were dependent on the in situ de novo production of the vector-encoded antigens. Challenge of mice vaccinated with these amplicons with a high dose of live virus, resulted in partial protection, with a significant reduction of viremia. This work highlights the potential use of a HSV-1 amplicon vector platform for generation of safe genetic vaccines.
authors.affiliation: Centro de Virología Animal (CEVAN-CONICET), Instituto de Ciencia y Tecnología Dr. Cesar Milstein, Saladillo 2468, C1440FFX, Ciudad de Buenos Aires, Argentina.
authors.forename: Alejandra
authors.initials: A
authors.lastname: D'Antuono
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Laimbacher
authors.forename: Jose
authors.initials: J
authors.lastname: La Torre
authors.forename: Virginia
authors.initials: V
authors.lastname: Tribulatti
authors.forename: Carina
authors.initials: C
authors.lastname: Romanutti
authors.forename: Patricia
authors.initials: P
authors.lastname: Zamorano
authors.forename: Valeria
authors.initials: V
authors.lastname: Quattrocchi
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Schraner
authors.forename: Mathias
authors.initials: M
authors.lastname: Ackermann
authors.forename: Cornel
authors.initials: C
authors.lastname: Fraefel
authors.forename: Nora
authors.initials: N
authors.lastname: Mattion
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000096:biosynthesis / Q000276:immunology; D036022:Capsid Proteins / Q000096:biosynthesis / Q000276:immunology; D002522:Chlorocebus aethiops; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D057809:HEK293 Cells; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D019076:Transgenes; D019444:Vaccines, DNA / Q000096:biosynthesis / Q000276:immunology*; D014709:Vero Cells; D014765:Viral Vaccines / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D019444:Vaccines, DNA; D014765:Viral Vaccines