GeoVax Inc., Smyrna, GA, USA.
Hum Vaccin Immunother. 2012 Nov 1;8(11):1654-8. doi: 10.4161/hv.21978. Epub 2012 Oct 30.
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.
在这里，我们报告了 GEO-D03，这是一种 DNA 疫苗，它共表达了非感染性 HIV-1 病毒样颗粒（VLPs）和人类细胞因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）。病毒样颗粒展示了 HIV-1 包膜糖蛋白（Env）的天然 gp160 形式，旨在诱导针对病毒和病毒感染细胞上天然形式的 Env 的抗体。DNA 表达的 HIV Gag、Pol 和 Env 蛋白也有可能引发针对病毒的特异性 CD4 和 CD8 T 细胞。共表达 GM-CSF 的目的是靶向一种细胞因子，该细胞因子可招募、扩增和分化巨噬细胞和树突状细胞到 VLP 表达部位。GEO-D03 DNA 疫苗目前已进入人体试验，作为重组改良安卡拉痘苗（MVA）增强剂的基础。在使用 SIV 原型疫苗的灵长类动物的临床前研究中，这种疫苗接种方案引发了抗病毒 T 细胞和抗体，在 12 周的每周直肠暴露中提供了 70%的预防获得性感染的保护作用，而使用的是异源 SIV。在挑战病毒中，Env 特异性 Ab 对 Env 天然形式的高亲和力与 SIV 感染的可能性降低相关。
