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Critical Reviews™ in Immunology
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ISSN Imprimer: 1040-8401
ISSN En ligne: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v30.i3.10
pages 223-237

Development of Safe and Effcacious Viral Vaccines for Animals

Tilahun Yilma
International Laboratory of Molecular Biology for Tropical Disease Agents, School of Veterinary Medicine, and Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, California
Paulo Verardi
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, Connecticut
Leslie Jones
International Laboratory of Molecular Biology for Tropical Disease Agents, School of Veterinary Medicine, University of California, Davis, California

RÉSUMÉ

We have taken a number of approaches to improve the safety and efficacy of recombinant vaccines for use in humans and animals, including: choice of the strain of vaccinia virus (VACV) used as a vector, insertional inactivation of virulence and immunoregulatory genes of VACV, and expression of cytokine genes that attenuate the vector by more than a million-fold without reduction in immunogenicity. These strategies are illustrated by providing examples of recombinant VACV (rVACV) vaccines we have developed for rinderpest, vesicular stomatitis, simian immunodeficiency virus, and smallpox. We constructed rVACVs expressing interferon-gamma (IFN -γ) and lacking the immune-modulating genes B8R, B13R, and B22R. IFN-γ is a cytokine with potent immunoregulatory, antineoplastic, and antiviral properties. These rVACVs 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 co-expression and the inactivation of one or more VACV immune-modulating genes provide an optimized method for increasing the safety while maintaining the efficacy of rVACV vaccines for use in humans and animals.


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