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    HIV-1 ENV DNA VACCINE PLUS PROTEIN BOOST
    7.
    发明公开
    HIV-1 ENV DNA VACCINE PLUS PROTEIN BOOST 审中-公开

    公开(公告)号：EP3964231A1

    公开(公告)日：2022-03-09

    申请号：EP21175121.9

    申请日：2014-11-06

    申请人： Inovio Pharmaceuticals, Inc. ,  The Trustees of The University of Pennsylvania

    发明人： WEINER, David B. ,  MUTHUMANI, Karuppiah ,  WISE, Megan ,  YAN, Jian ,  BRODERICK, Kate

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

    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.

    HIV-1 ENV DNA VACCINE PLUS PROTEIN BOOST
    9.
    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：EP3068427A1

    公开(公告)日：2016-09-21

    申请号：EP14861787.1

    申请日：2014-11-06

    申请人： The Trustees of The University of Pennsylvania ,  Inovio Pharmaceuticals, Inc.

    发明人： WEINER, David, B. ,  MUTHUMANI, Karuppiah ,  WISE, Megan ,  YAN, Jian ,  BRODERICK, Kate

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

    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 gpl40 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疫苗将很可能需要诱导强烈的T细胞应答，广泛中和抗体（bNAb）和引发抗体依赖性细胞毒性（ADCC）。 在此之前，我们利用自适应电穿孔（EP）递送的合成共有DNA免疫原证明了在猕猴和人体中诱导强烈的HIV / SIV细胞免疫应答。 然而，这种改进的DNA方法引发相关抗体应答的能力尚未被研究过。 在这里，我们调查在DNA总蛋白加强疫苗方案中编码来自HIV-1亚型A，B，C和D的gp140序列的共有DNA构建体的免疫原性。 小鼠和豚鼠通过EP用单和多分支DNA引发，并用重组gp120蛋白加强。 分析血清的gp120结合并诱导中和抗体活性。 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，合成的DNA初免蛋白加强方案诱导显着更高的抗体结合效价。 此外，来自DNA主蛋白加强组的血清能够中和一系列1级进化支B病毒以及多个1级进化枝A和进化枝C病毒中的更广泛范围的病毒。 进一步研究合成的DNA初免+自适应EP加蛋白加强似乎是必要的。