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Vaccinia Viruses with a Serpin Gene Deletion and Expressing IFN-γ Induce Potent Immune Responses without Detectable Replication in vivo
Fatema A. Legrand, Paulo H. Verardi, Kenneth S. Chan, Yue Peng, Leslie A. Jones and Tilahun D. Yilma
Proceedings of the National Academy of Sciences of the United States of America
Vol. 102, No. 8 (Feb. 22, 2005), pp. 2940-2945
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/3374725
Page Count: 6
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In a continuing effort to develop safe and efficacious vaccine and immunotherapeutic vectors, we constructed recombinant vaccinia virus (rVV) vaccines lacking either the B13R (SPI-2) or the B22R (SPI-1) immune-modulating gene and coexpressing IFN-γ. B13R and B22R are nonessential VV immune-modulating genes that have antiapoptotic and antiinflammatory properties with sequence homology to serine protease inhibitors (serpins). IFN-γ is a cytokine with potent immunoregulatory, antineoplastic, and antiviral properties. We observed that these rVVs with a deletion in a serpin gene and expressing IFN-γ replicated to high titers in tissue culture yet were avirulent in both immunocompromised and immunocompetent mice with no detectable viral replication in these animals. A single immunization elicited potent humoral, T helper, and cytotoxic T cell immune responses in mice despite the absence of any detectable virus replication in vivo. IFN-γ coexpression and the inactivation of one or more VV immune-modulating genes provide an optimized method for increasing the safety while maintaining the efficacy of rVV vaccines. This strategy provides a method for developing highly safe and efficacious vaccines for smallpox and other diseases and immunotherapeutic vectors.
Proceedings of the National Academy of Sciences of the United States of America © 2005 National Academy of Sciences