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    HIV-1 ENV DNA VACCINE PLUS PROTEIN BOOST
    5.
    发明公开
    HIV-1 ENV DNA VACCINE PLUS PROTEIN BOOST 审中-公开
    HIV-1 ENV DNA VACCINE PLUS蛋白质增加

    公开(公告)号：EP3068427A4

    公开(公告)日：2016-09-21

    申请号：EP14861787

    申请日：2014-11-06

    申请人： UNIV PENNSYLVANIA ,  INOVIO PHARMACEUTICALS INC

    发明人： WEINER DAVID B ,  MUTHUMANI KARUPPIAH ,  WISE MEGAN ,  YAN JIAN ,  BRODERICK KATE

    IPC分类号： A61K39/21 ,  C07K14/16 ,  C12P19/34

    CPC分类号： A61K39/21 ,  A61K39/12 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/57 ,  A61K2039/575 ,  A61K2039/70 ,  C07K14/005 ,  C12N7/00 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16171

    摘要： The present invention is directed to an effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs), and the elicitation of antibody-dependent cellular cytotoxicity (ADCC). Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP). However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime protein boost vaccine regimen. Mice and Guinea pigs were primed with single and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast the synthetic DNA prime protein boost protocol was induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime+adaptive EP plus protein boost appears warranted.

    摘要翻译： 本发明涉及有效的HIV疫苗很可能需要诱导强T细胞应答，广泛中和抗体（bNAb）以及诱导抗体依赖性细胞毒性（ADCC）。 以前，我们通过使用通过自适应电穿孔（EP）递送的合成共识DNA免疫原，证明了在猕猴和人类中诱导强烈的HIV / SIV细胞免疫应答。 然而，这种改进的DNA方法为相关抗体反应引发的能力以前没有被研究过。 在这里，我们调查编码来自HIV-1亚型A，B，C和D的gp140序列的DNA初步蛋白增强疫苗方案的共有DNA构建体的免疫原性。 小鼠和豚鼠用单次和多次进化枝DNA通过EP引发，并用重组gp120蛋白加强。 分析血清中的gp120结合和中和抗体活性的诱导。 用重组Env蛋白单独免疫诱导具有有限中和呼吸的低滴度结合抗体。 相比之下，合成DNA初始蛋白增强方案诱导显着更高的抗体结合滴度。 此外，来自DNA初始蛋白增强组的血清能够在1级进化枝B病毒以及多个1级进化枝A和进化枝C病毒的小组中中和更广泛的病毒。 进一步研究合成DNA素+自适应EP加蛋白质增强似乎是有必要的。