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    Enhanced first generation adenovirus vaccines expressing codon optimized HIV1-gag, pol, nef and modifications
    2.
    发明授权
    Enhanced first generation adenovirus vaccines expressing codon optimized HIV1-gag, pol, nef and modifications 失效
    增强的第一代腺病毒疫苗表达密码子优化的HIV1-gag，pol，nef和修饰

    公开(公告)号：US06733993B2

    公开(公告)日：2004-05-11

    申请号：US09952060

    申请日：2001-09-14

    申请人： Emilio A. Emini ,  Rima Youil ,  Andrew J. Bett ,  Ling Chen ,  David C. Kaslow ,  John W. Shiver ,  Timothy J. Toner ,  Danilo R. Casimiro

    发明人： Emilio A. Emini ,  Rima Youil ,  Andrew J. Bett ,  Ling Chen ,  David C. Kaslow ,  John W. Shiver ,  Timothy J. Toner ,  Danilo R. Casimiro

    IPC分类号： C12P2106

    CPC分类号： C12N7/00 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/545 ,  A61K2039/57 ,  C07K14/005 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2710/10351 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16322 ,  C12N2740/16334 ,  C12N2830/42

    摘要： First generation adenoviral vectors and associated recombinant adenovirus-based HIV vaccines which show enhanced stability and growth properties and greater cellular-mediated immunity are described within this specification. These adenoviral vectors are utilized to generate and produce through cell culture various adenoviral-based HIV-1 vaccines which contain HIV-1 gag, HIV-1 pol and/or HIV-1 nef polynucleotide pharmaceutical products, and biologically relevant modifications thereof. These adenovirus vaccines, when directly introduced into living vertebrate tissue, preferably a mammalian host such as a human or a non-human mammal of commercial or domestic veterinary importance, express the HIV1-Gag, Pol and/or Nef protein or biologically modification thereof, inducing a cellular immune response which specifically recognizes HIV-1. The exemplified polynucleotides of the present invention are synthetic DNA molecules encoding HIV-1 Gag, encoding codon optimized HIV-1 Pol, derivatives of optimized HIV-1 Pol (including constructs wherein protease, reverse transcriptase, RNAse H and integrase activity of HIV-1 Pol is inactivated), HIV-1 Nef and derivatives of optimized HIV-1 Nef, including nef mutants which effect wild type characteristics of Nef, such as myristylation and down regulation of host CD4. The adenoviral vaccines of the present invention, when administered alone or in a combined modality regime, will offer a prophylactic advantage to previously uninfected individuals and/or provide a therapeutic effect by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV-1 infection.

    摘要翻译： 在本说明书中描述了显示增强的稳定性和生长特性以及更大的细胞介导的免疫的第一代腺病毒载体和相关重组腺病毒的HIV疫苗。 这些腺病毒载体用于通过细胞培养产生和产生各种含有HIV-1 gag，HIV-1 pol和/或HIV-1 nef多核苷酸药物产品的基于腺病毒的HIV-1疫苗及其生物相关的修饰。 这些腺病毒疫苗当直接引入活的脊椎动物组织中时，优选哺乳动物宿主例如具有商业或家庭兽医重要性的人或非人哺乳动物，表达HIV1-Gag，Pol和/或Nef蛋白或其生物修饰， 诱导特异性识别HIV-1的细胞免疫应答。 本发明的示例性多核苷酸是编码HIV-1Gag的编码密码子优化的HIV-1 Pol的合成DNA分子，其优化的HIV-1 Pol的衍生物（包括其中蛋白酶，逆转录酶，RNAse H和HIV-1的整合酶活性 Pol被灭活），HIV-1 Nef和优化的HIV-1 Nef的衍生物，包括影响Nef野生型特征的nef突变体，如主体CD4的肉豆蔻酰化和下调。 本发明的腺病毒疫苗当单独施用或以组合的方式给药时，将对先前未感染的个体提供预防优势，和/或通过减少被感染个体内的病毒载量水平提供治疗效果，从而延长无症状期 HIV-1感染。

    Human antibodies interacting with HIV gp41
    10.
    发明授权
    Human antibodies interacting with HIV gp41 有权
    人类抗体与HIV gp41相互作用

    公开(公告)号：US07744887B2

    公开(公告)日：2010-06-29

    申请号：US11628164

    申请日：2005-05-31

    申请人： John W. Shiver ,  Michael D. Miller ,  Romas Geleziunas ,  Daria J. Hazuda ,  Peter S. Kim ,  Debra M. Eckert ,  Michael J. Root ,  Simon N. Lennard ,  Elisabetta Bianchi

    发明人： John W. Shiver ,  Michael D. Miller ,  Romas Geleziunas ,  Daria J. Hazuda ,  Peter S. Kim ,  Debra M. Eckert ,  Michael J. Root ,  Simon N. Lennard ,  Elisabetta Bianchi

    IPC分类号： A61K39/42 ,  G01N33/53 ,  A61K39/395 ,  C12P16/00

    CPC分类号： G01N33/56988 ,  C07K16/1063 ,  C07K2317/21 ,  C07K2317/622 ,  C07K2317/76 ,  G01N2500/00

    摘要： Human scFvs are disclosed which interact with a conformational epitope along the pre-hairpin, N-helix coiled coil structure within the heptad repeat 1 (HR1) region of gp41 of HIV. These antibodies, as well as IgG conversions, are shown to neutralize diverse HIV isolates. Isolated nucleic acid molecules are also disclosed which encode relevant portions of these antibodies, as well as the purified forms of the expressed antibodies or relevant antibody fragments, such as VH and VL chains. The antibody compositions disclosed within this specification may provide for a therapeutic treatment against HIV infection by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV infection. These antibodies will also be useful in assays to identify HIV antiviral compounds as well as allowing for the identification of candidate HIV vaccines, such as HIV peptide vaccines.

    摘要翻译： 披露了人scFv，其与艾滋病病毒gp41的七重复重复1（HR1）区域内的前发夹，N-螺旋卷曲螺旋结构与构象表位相互作用。 显示出这些抗体以及IgG转化中和多种HIV分离物。 还公开了分离的核酸分子，其编码这些抗体的相关部分，以及所表达的抗体或相关抗体片段（例如VH和VL链）的纯化形式。 在本说明书中公开的抗体组合物可通过降低受感染个体内的病毒载量水平来提供抗HIV感染的治疗性治疗，从而延长HIV感染的无症状期。 这些抗体也可用于鉴定HIV抗病毒化合物的测定，以及允许鉴定候选的HIV疫苗，例如HIV肽疫苗。