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    Incapacitated whole-cell immunogenic bacterial compositions produced by recombinant expression
    3.
    发明授权
    Incapacitated whole-cell immunogenic bacterial compositions produced by recombinant expression 有权
    通过重组表达产生的无效的全细胞免疫原性细菌组合物

    公开(公告)号：US09289481B2

    公开(公告)日：2016-03-22

    申请号：US12560321

    申请日：2009-09-15

    申请人： Janakiraman Ramachandran ,  Sriram Padmanabhan ,  Bharathi Sriram

    发明人： Janakiraman Ramachandran ,  Sriram Padmanabhan ,  Bharathi Sriram

    IPC分类号： A61K39/02 ,  A61P37/04 ,  C12N15/74 ,  A61K39/108 ,  A61K39/00

    CPC分类号： A61K39/02 ,  A61K39/0258 ,  A61K2039/522 ,  C12N15/70 ,  Y02A50/474

    摘要： The present invention features incapacitated whole-cell bacterial immunogenic compositions and methods of their production, which compositions are useful to deliver antigens in a manner resembling the live infectious organism in terms of elicitation of a robust immune response, but with reduced risk or no risk of disease. The compositions of the invention are produced by rendering a bacterium bacteriostatic through expression of a recombinant promoter in the bacterial cell, which promoter can be operably linked to a polynucleotide encoding a recombinant gene product. In one embodiment, where the bacterium is a gram negative host, the recombinant gene product provides for reduced toxicity of LPS. In one embodiment, the gene product is a bacteriophage protein, such as endolysin, holin, or ndd.

    摘要翻译： 本发明具有丧失能力的全细胞细菌免疫原性组合物及其生产方法，该组合物可用于以类似于活的感染性生物体的方式递送抗原，以引发强大的免疫应答，但具有降低的风险或没有风险 疾病。 本发明的组合物通过使细菌抑菌细菌通过在细菌细胞中表达重组启动子而产生，该启动子可以与编码重组基因产物的多核苷酸可操作地连接。 在一个实施方案中，当细菌是革兰氏阴性宿主时，重组基因产物提供LPS的毒性降低。 在一个实施方案中，基因产物是噬菌体蛋白，例如细胞内溶素，蛋白质或ndd。

    Lysin-deficient bacteriophages having reduced immunogenicity
    8.
    发明申请
    Lysin-deficient bacteriophages having reduced immunogenicity 有权
    具有降低免疫原性的赖氨酸缺陷型噬菌体

    公开(公告)号：US20050226851A1

    公开(公告)日：2005-10-13

    申请号：US11053982

    申请日：2005-02-08

    申请人： Janakiraman Ramachandran ,  Sriram Padmanabhan ,  Bharathi Sriram

    发明人： Janakiraman Ramachandran ,  Sriram Padmanabhan ,  Bharathi Sriram

    IPC分类号： C12N15/09 ,  A61K9/19 ,  A61K35/76 ,  A61P31/04 ,  C12N1/21 ,  C12N7/00 ,  C12N7/01 ,  C12N7/04 ,  A61K45/00

    CPC分类号： C12N7/00 ,  A61K35/76 ,  C12N2795/10111 ,  C12N2795/10132 ,  C12N2795/10161 ,  Y02A50/475

    摘要： The present invention features therapeutic bacteriophage deficient in the lysin protein (“Lys minus” phage). Lys minus bacteriophage are incapable of facilitating efficient lysis of the bacterial host since the enzymatic activity of the lysin of the phage is needed for breaking down the peptidoglycan layer of the bacterial cell wall. Lys minus bacteriophage retain activity in invasion of its appropriate bacterial host, destruction of the bacterial genome, and replication, which are sufficient to inhibit bacterial growth and replication. Therefore, the therapeutic Lys minus phage stops the spread of infection by the bacterial pathogen without lysis of the bacterium. This approach is attractive as it also prevents the release of the phage progeny, thus reducing or eliminating the potential for generation of immune responses against the phage. The incapacitated bacterial pathogen is then removed by the normal defense systems such as phagocytes and macrophages.

    摘要翻译： 本发明的特征在于溶酶蛋白（“Lys减”噬菌体）中缺乏的治疗性噬菌体。 Lys minus噬菌体不能促进细菌宿主的有效溶解，因为需要噬菌体溶素的酶活性来分解细菌细胞壁的肽聚糖层。 Lys减去噬菌体在其适当的细菌宿主的侵入中保留活性，破坏细菌基因组和复制，其足以抑制细菌生长和复制。 因此，治疗性Lys-噬菌体阻止了细菌病原体感染的扩散，而不会破坏细菌。 这种方法是有吸引力的，因为它也可以防止噬菌体后代的释放，从而减少或消除针对噬菌体产生免疫应答的可能性。 然后通过正常的防御系统如吞噬细胞和巨噬细胞去除失能的细菌病原体。