公开(公告)号：US09566329B2

公开(公告)日：2017-02-14

申请号：US14387514

申请日：2013-04-08

申请人： The United States of America, as Represented by the Secretary, Department of Health and Human Services

发明人： Ira Berkower ,  Konstantin Virnik

IPC分类号： A61K39/21 ,  C12N15/86 ,  A61K39/12 ,  A61K39/00

CPC分类号： A61K39/21 ,  A61K39/12 ,  A61K2039/53 ,  A61K2039/54 ,  A61K2039/545 ,  C12N15/86 ,  C12N2740/15034 ,  C12N2740/16034 ,  C12N2740/16134 ,  C12N2770/36221 ,  C12N2770/36234 ,  C12N2770/36243 ,  C12N2770/36271

摘要： Disclosed herein are isolated rubella viral vector constructs that include a rubella non-structural protein open reading frame (ORF) without an in-frame deletion, a rubella structural protein ORF, and a heterologous antigenic insert. In one example, the heterologous antigenic insert is positioned within the rubella structural protein ORF. In some examples, the heterologous antigenic insert is positioned in the rubella structural protein ORF in between a gene encoding structural protein E2 and a gene encoding structural protein E1. Exemplary antigenic inserts include HIV, SIV, RSV or hepatitis B surface antigens. In some examples, the HIV antigenic insert is a Gag antigenic insert, a gp41 antigenic insert or a gp120 antigenic insert. Also disclosed are uses of the isolated rubella viral vector, such as to induce an immune response to a particular virus, such as HIV-1, testing sensitivity to neutralizing antibodies, or screening antiviral drugs (such as protease inhibitors).

摘要翻译： 本文公开了分离的风疹病毒载体构建体，其包含不含框内缺失的风疹非结构蛋白质开放阅读框（ORF），风疹结构蛋白ORF和异源抗原插入物。 在一个实例中，异源抗原插入物位于风疹结构蛋白ORF内。 在一些实例中，异源抗原插入物位于编码结构蛋白E2的基因和编码结构蛋白E1的基因之间的风疹结构蛋白ORF中。 示例性抗原插入物包括HIV，SIV，RSV或乙型肝炎表面抗原。 在一些实例中，HIV抗原插入物是Gag抗原插入物，gp41抗原插入片段或gp120抗原插入物。 还公开了分离的风疹病毒载体的用途，例如诱导对特定病毒（例如HIV-1）的免疫应答，测试对中和抗体的敏感性，或筛选抗病毒药物（例如蛋白酶抑制剂）。

公开(公告)号：US09266928B2

公开(公告)日：2016-02-23

申请号：US14089460

申请日：2013-11-25

申请人： The United States of America, as Represented by the Secretary, Department of Health and Human Services

发明人： Ira Berkower

IPC分类号： C07H21/04 ,  A61K39/21 ,  C07K14/005 ,  C07K16/10 ,  A61K39/12 ,  A61K39/00

CPC分类号： C07K14/005 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/5258 ,  A61K2039/545 ,  A61K2039/55505 ,  A61K2039/55561 ,  A61K2039/6075 ,  C07K16/1063 ,  C07K2317/76 ,  C12N2740/16122 ,  C12N2740/16134

摘要： Disclosed herein are isolated immunogens including variant gp120 polypeptides. In an example, a variant gp120 polypeptide includes a deletion of at least 8 consecutive residues of the fourth conserved loop (C4) between residues 419 and 434 of gp120 according to HXB2 numbering. Also provided are isolated nucleic acid molecules encoding the disclosed isolated immunogens. In an example, an isolated nucleic acid molecule further includes a nucleic acid molecule encoding a hepatitis B surface antigen or a variant thereof. Compositions including the isolated immunogens including variant gp120 polypeptides are also disclosed. In some examples, a composition further includes a carrier protein, such as a hepatitis B surface antigen or a variant thereof (natural or recombinant). Viral-like particles are also provided including any of the disclosed isolated immunogens or compositions. Also disclosed are uses of these variant gp120 polypeptides and nucleic acids encoding variant polypeptides, such as to induce an immune response to HIV-1.

摘要翻译： 本文公开了分离的免疫原，包括变体gp120多肽。 在一个实例中，变体gp120多肽包括根据HXB2编号在gp120的残基419和434之间的第四保守环（C4）的至少8个连续残基的缺失。 还提供了编码公开的分离的免疫原的分离的核酸分子。 在一个实例中，分离的核酸分子还包括编码乙型肝炎表面抗原或其变体的核酸分子。 还公开了包括分离的免疫原的组合物，包括变体gp120多肽。 在一些实例中，组合物还包括载体蛋白，例如乙型肝炎表面抗原或其变体（天然或重组）。 还提供病毒样颗粒，包括任何公开的分离的免疫原或组合物。 还公开了这些变体gp120多肽和编码变体多肽的核酸的用途，例如诱导对HIV-1的免疫应答。

公开(公告)号：US09486518B2

公开(公告)日：2016-11-08

申请号：US14642233

申请日：2015-03-09

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Services

发明人： Ira Berkower

IPC分类号： A61K39/00 ,  A61K39/29 ,  A61K39/21 ,  C07K14/005 ,  A61K39/12 ,  C12N7/00

CPC分类号： A61K39/292 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/5256 ,  A61K2039/5258 ,  A61K2039/54 ,  A61K2039/545 ,  A61K2039/55505 ,  A61K2039/55561 ,  A61K2039/57 ,  A61K2039/64 ,  A61K2039/645 ,  C07K14/005 ,  C07K2319/03 ,  C12N7/00 ,  C12N2730/10122 ,  C12N2730/10134 ,  C12N2740/15022 ,  C12N2740/15034 ,  C12N2740/16134 ,  C12N2740/16222 ,  C12N2740/16234

摘要： Disclosed herein are isolated immunogens including variant hepatitis B surface antigens (HBsAgs). In an example, a variant HBsAg includes a HBsAg with one or more transmembrane domains of the HBsAg replaced with a gp41 antigenic insert. The antigenic insert can include an antigenic polypeptide fragment of gp41 including the membrane proximal region of gp41 and a transmembrane membrane region of gp41. The replacement of a membrane spanning domain of HBsAg with a membrane spanning domain of gp41 anchors gp41 into HBsAg in virtually the identical orientation as on HIV virions and correctly orients the nearby MPR on the lipid layer. Thus, the disclosed variant HBsAgs display the neutralization-sensitive MPR in association with a lipid layer, while presenting it at the most immunogenic site on HBsAg. Also disclosed are uses of these variant HBsAgs, and nucleic acids encoding variant HBsAgs, such as to induce an immune response to HIV-1.

摘要翻译： 本文公开了分离的免疫原，包括变异型乙型肝炎表面抗原（HBsAg）。 在一个实例中，变体HBsAg包括具有用gp41抗原插入物取代的HBsAg的一个或多个跨膜结构域的HBsAg。 抗原插入物可以包括gp41的抗原多肽片段，其包括gp41的近膜区域和gp41的跨膜区域。 用gp41的跨膜结构域替换HBsAg的跨膜结构域，将gp41锚定到HBsAg中，与HIV病毒体几乎完全相同，并且正确定位在脂质层上的附近的MPR。 因此，所公开的变体HBsAg显示与脂质层相关联的中和敏感性MPR，同时将其呈现在HBsAg上最高免疫原性位点。 还公开了这些变体HBsAg和编码变体HBsAg的核酸的用途，例如诱导对HIV-1的免疫应答。