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J. Virol. doi:10.1128/JVI.01692-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Incorporation of GPI-anchored GM-CSF or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles

Department of Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd, Atlanta, GA 30322, Department of Pathology and Laboratory Medicine, Emory University School of Medicine

^* To whom correspondence should be addressed. Email: compans{at}microbio.emory.edu, skang2{at}emory.edu.

	Abstract

The rapid worldwide spread of HIV mandates the development of successful vaccination strategies. Since live attenuated HIV cannot be used 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 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 compared to 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, as 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 to VLPs can be a promising approach to augment the efficacy of VLP antigens.

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