HSV-1 amplicon vectors that direct the in situ production of heterologous antigens in mammalian cells may eventually be used for genetic immunization

D'ANTUONO, ALEJANDRA; LAIMBACHER, ANDREA; LA TORRE, JOSE; TRIBULATTI, VIRGINIA; ROMANUTTI, CARINA; ZAMORANO, PATRICIA; QUATTROCCHI, VALERIA; SCHRANER, ELIZABETH; ACKERMAN, MATHIAS; FRAEFEL, CORNEL; MATTION, NORA

VACCINE

ELSEVIER SCI LTD

Año: 2010 vol. 28 p. 7363 - 7372

0264-410X

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 highly 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 x 105 transducing units of amplicon vectors resulted in a 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. 10.1016/j.vaccine.2010.09.011