Open AccessIncorporation of Glycosylphosphatidylinositol-Anchored Granulocyte- MacrophageColony-Stimulating Factor or CD40 Ligand Enhances Immunogenicity of Chimeric Simian Immunodeficiency Virus-Like Particles
Author(s) -
Ioanna Skountzou,
FuShi Quan,
Sailaja Gangadhara,
Ling Ye,
Andrei N. Vzorov,
Periasamy Selvaraj,
Joshy Jacob,
Richard W. Compans,
SangMoo Kang
Publication year - 2007
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01692-06
Subject(s) - simian immunodeficiency virus , immunogenicity , virology , biology , virus like particle , immune system , cd40 , virus , antigen , vaccination , immunology , cytotoxic t cell , in vitro , recombinant dna , biochemistry , gene
Therapid worldwide spread of human immunodeficiency virus (HIV) mandatesthe development of successful vaccination strategies. Since liveattenuated HIV is not accepted as a vaccine due to safety concerns,virus-like particles (VLPs) offer an attractive safe alternativebecause they lack the viral genome yet they are perceived by the immunesystem as a virus particle. We hypothesized that addingimmunostimulatory signals to VLPs would enhance their efficacy. Toaccomplish 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 biologicalactivity and ability to enhance immune responses in vivo. Immunizationof mice with chimeric SIV VLPs containing GM-CSF induced SIVEnv-specific antibodies as well as neutralizing activity atsignificantly 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 eitherGM-CSF or CD40L showed significantly increased CD4+ -and CD8+ -T-cell responses to SIV Env, compared tostandard SIV VLPs. Taken together, these results demonstrate that theincorporation of immunostimulatory molecules enhances humoral andcellular immune responses. We propose that anchoring immunostimulatorymolecules into SIV VLPs can be a promising approach to augmenting theefficacy of VLPantigens.