Incorporation of glycosylphosphatidylinositol-anchored granulocyte- macrophage colony-stimulating factor or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles.
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.
Skountzou
Ioanna
I
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322, USA.
Quan
Fu-Shi
FS
Gangadhara
Sailaja
S
Ye
Ling
L
Vzorov
Andrei
A
Selvaraj
Periasamy
P
Jacob
Joshy
J
Compans
Richard W
RW
Kang
Sang-Moo
SM
D000818:Animals; D023201:CD40 Ligand / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002678:Chimera; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007313:Insecta; D016865:Reassortant Viruses / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D017261:Glycosylphosphatidylinositols; D023201:CD40 Ligand; D016178:Granulocyte-Macrophage Colony-Stimulating Factor