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Journal of Virology, February 2009, p. 1592-1601, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.01446-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Lower Levels of Gamma Interferon Expressed by a Pseudotyped Single-Cycle Simian Immunodeficiency Virus Enhance Immunogenicity in Rats{triangledown}

Yue Peng,1,{dagger} Fan-ching Lin,1 Paulo H. Verardi,1 Leslie A. Jones,1 and Tilahun D. Yilma1,2*

International Laboratory of Molecular Biology for Tropical Disease Agents, School of Veterinary Medicine,1 Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California 956162

Received 10 July 2008/ Accepted 2 December 2008

A vaccine for human immunodeficiency virus (HIV) infection is desperately needed to control the AIDS pandemic. To address this problem, we constructed single-cycle simian immunodeficiency viruses (SIVs) pseudotyped with the glycoprotein of vesicular stomatitis virus and expressing different levels of gamma interferon (IFN-{gamma}) as a potential vaccine strategy. We previously showed that IFN-{gamma} expression by pseudotyped SIVs does not alter viral single-cycle infectivity. T cells primed with dendritic cells transduced by pseudotyped SIVs expressing high levels of IFN-{gamma} had stronger T-cell responses than those primed with dendritic cells transduced by constructs lacking IFN-{gamma}. In the present study, we tested the immunogenicities of these pseudotyped SIVs in a rat model. The construct expressing low levels of rat IFN-{gamma} (dSIVLR{gamma}) induced higher levels of cell-mediated and humoral immune responses than the construct lacking IFN-{gamma} (dSIVR). Rats vaccinated with dSIVLR{gamma} also had lower viral loads than those vaccinated with dSIVR when inoculated with a recombinant vaccinia virus expressing SIV Gag-Pol as a surrogate challenge. The construct expressing high levels of IFN-{gamma} (dSIVHR{gamma}) did not further enhance immunity and was less protective than dSIVLR{gamma}. In conclusion, the data indicated that IFN-{gamma} functioned as an adjuvant to augment antigen-specific immune responses in a dose- and cell type-related manner in vivo. Thus, fine-tuning of the cytokine expression appears to be essential in designing vaccine vectors expressing adjuvant genes such as the gene for IFN-{gamma}. Furthermore, we provide evidence of the utility of the rat model to evaluate the immunogenicities of single-cycle HIV/SIV recombinant vaccines before initiating studies with nonhuman primate models.

* Corresponding author. Mailing address: International Laboratory of Molecular Biology for Tropical Disease Agents, University of California, Davis, CA 95616. Phone: (530) 752-8306. Fax: (530) 752-1354. E-mail: tdyilma{at}ucdavis.edu

{triangledown} Published ahead of print on 10 December 2008.

{dagger} Present address: Department of Urology, School of Medicine, Stanford University, Stanford, CA 94305.

Journal of Virology, February 2009, p. 1592-1601, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.01446-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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