Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine.
Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine.
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DOI：
10.4161/hv.21978
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发表时间：
2012-11-01
影响因子：
4.8
通讯作者：
Robinson HL
中科院分区：
文献类型：
--
作者：
Hellerstein M;Xu Y;Marino T;Lu S;Yi H;Wright ER;Robinson HL
在这里，我们报道GEO-D03，一种DNA疫苗，共同表达非传染性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）。病毒样颗粒显示HIV-1包膜糖蛋白（Env）的天然gp160形式，并设计用于在病毒和病毒感染细胞上引发针对自然形式Env的抗体。dna表达的HIV Gag、Pol和Env蛋白也有可能引发病毒特异性CD4和CD8 T细胞。共表达GM-CSF的目的是靶向募集、扩增和分化巨噬细胞和树突状细胞到VLP表达位点的细胞因子。GEO-D03 DNA疫苗目前已进入人体试验阶段，作为重组修饰安卡拉牛痘（MVA）增强剂的先导剂。在使用SIV原型疫苗对猕猴进行的临床前研究中，这种疫苗接种方案可激发抗病毒T细胞和抗体，并在每周12次的直肠接触异源SIV期间提供70%的保护。攻击病毒中Env的天然形式的Env特异性抗体的高亲切度与SIV感染的低可能性相关。
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.
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影响因子：
5.5
作者：
Schell, John B.;Bahl, Kapil;Rose, John K.
通讯作者：
Rose, John K.
影响因子：
5.5
作者：
Lai, Lilin;Kwa, Sue-Fen;Kozlowski, Pamela A.;Montefiori, David C.;Nolen, Tracy L.;Hudgens, Michael G.;Johnson, Welkin E.;Ferrari, Guido;Hirsch, Vanessa M.;Felber, Barbara K.;Pavlakis, George N.;Earl, Patricia L.;Moss, Bernard;Amara, Rama Rao;Robinson, Harriet L.
通讯作者：
Robinson, Harriet L.
影响因子：
11.2
作者：
Serafini, P;Carbley, R;Borrello, I
通讯作者：
Borrello, I
DOI：
10.1073/pnas.90.8.3539
发表时间：
1993-04-15
影响因子：
11.1
作者：
DRANOFF, G;JAFFEE, E;MULLIGAN, RC
通讯作者：
MULLIGAN, RC
影响因子：
5.4
作者：
PURCELL, DFJ;MARTIN, MA
通讯作者：
MARTIN, MA