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    • 7. 发明授权
    • Polynucleotide tuberculosis vaccine
    • 多核苷酸结核疫苗
    • US06384018B1
    • 2002-05-07
    • US09010733
    • 1998-01-22
    • Jean ContentKris HuygenMargaret A. LiuDonna MontgomeryJeffrey Ulmer
    • Jean ContentKris HuygenMargaret A. LiuDonna MontgomeryJeffrey Ulmer
    • A01N4304
    • A61K31/711A61K39/00A61K48/00A61K2039/51C07K14/35
    • Genes encoding Mycobacterium tuberculosis (M.tb) proteins were cloned into eukaryotic expression vectors to express the encoded proteins in mammalian muscle cells in vivo. Animals were immunized by injection of these DNA constructs, termed polynucleotide vaccines or PNV, into their muscles. Immune antisera was produced against M.tb antigens. Specific T-cell responses were detected in spleen cells of vaccinated mice and the profile of cytokine secretion in response to antigen 85 was indicative of a Th1 type of helper T-cell response (i.e., high IL-2 and IFN-&ggr;). Protective efficacy of an M.tb DNA vaccine was demonstrated in mice after challenge with M.bovis BCG, as measured by a reduction in mycobacterial multiplication in the spleens and lungs of M.tb DNA-vaccinated mice compared to control DNA-vaccinated mice or primary infection in naive mice.
    • 将编码结核分枝杆菌(M.tb)蛋白的基因克隆到真核表达载体中以在体内表达哺乳动物肌肉细胞中编码的蛋白质。 通过将这些DNA构建体(称为多核苷酸疫苗或PNV)注入其肌肉来免疫动物。 针对M.tb抗原产生免疫抗血清。 在接种疫苗的小鼠的脾细胞中检测到特异性T细胞应答,响应于抗原85的细胞因子分泌曲线表示Th1型辅助T细胞应答(即高IL-2和IFN-γ)。 在用M.bovis BCG攻击后的小鼠中证明了M.tb DNA疫苗的保护功效,如通过与对照DNA接种的小鼠相比,在接种M.tb DNA的小鼠的脾和肺中的分枝杆菌增殖减少所测量的 幼稚小鼠初次感染。