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Journal of Virology, February 2007, p. 1083-1094, Vol. 81, No. 3
0022-538X/07/$08.00+0     doi:10.1128/JVI.01692-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Incorporation of Glycosylphosphatidylinositol-Anchored Granulocyte- Macrophage Colony-Stimulating Factor or CD40 Ligand Enhances Immunogenicity of Chimeric Simian Immunodeficiency Virus-Like Particles{triangledown}

Ioanna Skountzou,1 Fu-Shi Quan,1 Sailaja Gangadhara,1 Ling Ye,1 Andrei Vzorov,1 Periasamy Selvaraj,2 Joshy Jacob,1 Richard W. Compans,1* and Sang-Moo Kang1*

Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, Georgia 30322,1 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia2

Received 4 August 2006/ Accepted 2 November 2006

The rapid worldwide spread of human immunodeficiency virus (HIV) mandates the development of successful vaccination strategies. Since live attenuated HIV is not accepted as a vaccine due to safety concerns, virus-like particles (VLPs) offer an attractive safe alternative because they lack the viral genome yet they are perceived by the immune system as a virus particle. We hypothesized that adding immunostimulatory signals to VLPs would enhance their efficacy. To accomplish this we generated chimeric simian immunodeficiency virus (SIV) VLPs containing either glycosylphosphatidylinositol (GPI)-anchored granulocyte-macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity and ability to enhance immune responses in vivo. Immunization of mice with chimeric SIV VLPs containing GM-CSF induced SIV Env-specific antibodies as well as neutralizing activity at significantly higher levels than those induced by standard SIV VLPs, SIV VLPs containing CD40L, or standard VLPs mixed with soluble GM-CSF. In addition, mice immunized with chimeric SIV VLPs containing either GM-CSF or CD40L showed significantly increased CD4+- and CD8+-T-cell responses to SIV Env, compared to standard SIV VLPs. Taken together, these results demonstrate that the incorporation of immunostimulatory molecules enhances humoral and cellular immune responses. We propose that anchoring immunostimulatory molecules into SIV VLPs can be a promising approach to augmenting the efficacy of VLP antigens.

* Corresponding author. Mailing address: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322. Phone for Richard W. Compans: (404) 727-5950. Fax: (404) 727-8250. E-mail: compans{at}microbio.emory.edu. Phone for Sang-Moo Kang: (404) 727-3228. Fax: (404) 727-3659. E-mail: skang2{at}emory.edu.

{triangledown} Published ahead of print on 15 November 2006.

Journal of Virology, February 2007, p. 1083-1094, Vol. 81, No. 3
0022-538X/07/$08.00+0     doi:10.1128/JVI.01692-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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  • Metzner, C., Mostegl, M. M., Gunzburg, W. H., Salmons, B., Dangerfield, J. A. (2008). Association of glycosylphosphatidylinositol-anchored protein with retroviral particles. FASEB J. 22: 2734-2739 [Abstract] [Full Text]  


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