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Role of Genes That Modulate Host Immune Responses in the Immunogenicity and Pathogenicity of Vaccinia Virus

Shawn S. Jackson,¹ Petr Ilyinskii,^2, Valérie Philippon,² Linda Gritz,² Alicia Gómez Yafal,² Kimberly Zinnack,² Kristin R. Beaudry,¹ Kelledy H. Manson,² Michelle A. Lifton,¹ Marcelo J. Kuroda,¹ Norman L. Letvin,^1* Gail P. Mazzara,² and Dennis L. Panicali²

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,¹ Therion Biologics Corporation, Cambridge, Massachusetts 02142²

Received 26 September 2004/ Accepted 3 January 2005

Poxvirus vaccine vectors, although capable of eliciting potent immune responses, pose serious health risks in immunosuppressed individuals. We therefore constructed five novel recombinant vaccinia virus vectors which contained overlapping deletions of coding regions for the B5R, B8R, B12R, B13R, B14R, B16R, B18R, and B19R immunomodulatory gene products and assessed them for both immunogenicity and pathogenicity. All five of these novel vectors elicited both cellular and humoral immunity to the inserted HIV-BH10 env comparable to that induced by the parental Wyeth strain vaccinia virus. However, deletion of these immunomodulatory genes did not increase the immunogenicity of these vectors compared with the parental vaccinia virus. Furthermore, four of these vectors were slightly less virulent and one was slightly more virulent than the Wyeth strain virus in neonatal mice. Attenuated poxviruses have potential use as safer alternatives to current replication-competent vaccinia virus. Improved vaccinia virus vectors can be generated by deleting additional genes to achieve a more significant viral attenuation.

Present address: Hematology/Oncology Division, Beth Israel Deaconess Medical Center, HIM Building, Room 1044, 330 Brookline Avenue, Boston, MA 02215.