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    • 2. 发明授权
    • Enhanced first generation adenovirus vaccines expressing codon optimized HIV1-gag, pol, nef and modifications
    • 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
    • US06733993B2
    • 2004-05-11
    • US09952060
    • 2001-09-14
    • Emilio A. EminiRima YouilAndrew J. BettLing ChenDavid C. KaslowJohn W. ShiverTimothy J. TonerDanilo R. Casimiro
    • Emilio A. EminiRima YouilAndrew J. BettLing ChenDavid C. KaslowJohn W. ShiverTimothy J. TonerDanilo R. Casimiro
    • C12P2106
    • C12N7/00A61K2039/5256A61K2039/53A61K2039/545A61K2039/57C07K14/005C12N15/86C12N2710/10343C12N2710/10351C12N2740/16122C12N2740/16134C12N2740/16322C12N2740/16334C12N2830/42
    • 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.
    • 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。