title: Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine.
abstract: Here, we report on GEO-D03, a DNA vaccine that co-expresses non-infectious HIV-1 virus-like particles (VLPs) and the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The virus-like particles display the native gp160 form of the HIV-1 Envelope glycoprotein (Env) and are designed to elicit antibody against the natural form of Env on virus and virus-infected cells. The DNA-expressed HIV Gag, Pol and Env proteins also have the potential to elicit virus-specific CD4 and CD8 T cells. The purpose of the co-expressed GM-CSF is to target a cytokine that recruits, expands and differentiates macrophages and dendritic cells to the site of VLP expression. The GEO-D03 DNA vaccine is currently entered into human trials as a prime for a recombinant modified vaccinia Ankara (MVA) boost. In preclinical studies in macaques using an SIV prototype vaccine, this vaccination regimen elicited both anti-viral T cells and antibody, and provided 70% protection against acquisition during 12 weekly rectal exposures with a heterologous SIV. Higher avidity of the Env-specific Ab for the native form of the Env in the challenge virus correlated with lower likelihood of SIV infection.
authors.affiliation: GeoVax Inc., Smyrna, GA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hellerstein
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Xu
authors.forename: Tracie
authors.initials: T
authors.lastname: Marino
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Wright
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D016207:Cytokines; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: DNA vaccine; GEO-D03 DNA vaccine; GM-CSF adjuvant; HIV vaccine; HIV virus-like particles