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, Tilahun Yilma

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2940-2945
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number8
DOIs
StatePublished - Feb 22 2005

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Serine Proteinase Inhibitors
Vaccinia virus
Gene Deletion
Vaccines
Genes
Smallpox Vaccine
Disease Vectors
Virus Replication
Sequence Homology
Helper-Inducer T-Lymphocytes
Antineoplastic Agents
Antiviral Agents
Immunization
Anti-Inflammatory Agents
Cytokines
Safety

Keywords

  • Efficacy immune-modulating genes
  • Safety
  • Smallpox
  • Vaccines

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Vaccinia viruses with a serpin gene deletion and expressing IFN-γ induce potent immune responses without detectable replication in vivo. / Legrand, Fatema A.; Verardi, Paulo H.; Chan, Kenneth S.; Peng, Yue; Jones, Leslie A.; Yilma, Tilahun.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 8, 22.02.2005, p. 2940-2945.

Research output: Contribution to journalArticle

Legrand, Fatema A. ; Verardi, Paulo H. ; Chan, Kenneth S. ; Peng, Yue ; Jones, Leslie A. ; Yilma, Tilahun. / Vaccinia viruses with a serpin gene deletion and expressing IFN-γ induce potent immune responses without detectable replication in vivo. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 8. pp. 2940-2945.
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