Attenuated poxviruses expressing a synthetic HIV protein stimulate HLA-A2-restricted cytotoxic T-cell responses
Attenuated poxviruses expressing a synthetic HIV protein stimulate HLA-A2-restricted cytotoxic T-cell responses
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DOI：
10.1016/j.vaccine.2004.02.025
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发表时间：
2004-09-03
期刊：
影响因子：
5.5
通讯作者：
Sirard, JC
中科院分区：
文献类型：
--
作者：
Didierlaurent, A;Ramirez, JC;Sirard, JC
有效的HIV疫苗必须触发针对各种病毒抗原的细胞介导的免疫。然而，人们对携带多种蛋白质的疫苗诱导的反应的广度知之甚少。在这里，我们报告的免疫原性的构建体窝藏的HIV-1 IIIB的gag，pol和nef基因（gpn）的融合设计的最佳安全性和等摩尔表达的HIV蛋白。携带gpn构建体的减毒痘病毒MVA和NYVAC在常规小鼠中诱导有效的免疫应答，其特征在于刺激Gpn特异性IFN-γ产生细胞和细胞毒性T细胞。在HLA-A2转基因小鼠中，重组MVA引起针对大多数HLA-A2（+）HIV-1感染个体识别的表位的细胞毒性反应。我们还发现，MVA疫苗触发了从HIV-1血清阳性患者分离的外周血细胞的体外扩增，并且具有与免疫HLA-A2转基因小鼠相似的特异性。总之，由MVA递送的合成HIV多抗原Gpn是免疫原性的，由人MHC I类分子有效加工和呈递。(C)2004爱思唯尔有限公司保留所有权利。
Efficient HIV vaccines have to trigger cell-mediated immunity directed against various viral antigens. However little is known about the breadth of the response induced by vaccines carrying multiple proteins. Here, we report on the immunogenicity of a construct harbouring a fusion of the HIV-1 IIIB gag, pol and nef genes (gpn) designed for optimal safety and equimolar expression of the HIV proteins. The attenuated poxviruses, MVA and NYVAC, harbouring the gpn construct, induced potent immune responses in conventional mice characterised by stimulation of Gpn-specific IFN-gamma-producing cells and cytotoxic T cells. In HLA-A2 transgenic mice, recombinant MVA elicited cytotoxic responses against epitopes recognised in most HLA-A2(+) HIV-1-infected individuals. We also found that the MVA vaccine triggered the in vitro expansion of peripheral blood cells isolated from a HIV-1-seropositive patient and with similar specificity as found in immunised HLA-A2 transgenic mice. In conclusion, the synthetic HIV polyantigen Gpn delivered by MVA is immunogenic, efficiently processed and presented by human MHC class I molecules. (C) 2004 Elsevier Ltd. All rights reserved.