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    Protein complex system for increased immunogenicity and functionality, and methods making and use
    4.
    发明授权
    Protein complex system for increased immunogenicity and functionality, and methods making and use 有权
    增加免疫原性和功能的蛋白质复合体系，以及制备和使用方法

    公开(公告)号：US09562077B2

    公开(公告)日：2017-02-07

    申请号：US13803057

    申请日：2013-03-14

    Applicant: Children's Hospital Medical Center

    Inventor： Ming Tan ,  Xi Jiang ,  Leyi Wang

    IPC: C07K14/005 ,  A61K39/12 ,  A61K39/385 ,  A61K39/00

    CPC classification number: C07K14/005 ,  A61K39/12 ,  A61K39/385 ,  A61K2039/543 ,  A61K2039/627 ,  A61K2039/64 ,  A61K2039/70 ,  C07K2319/23 ,  C07K2319/40 ,  C07K2319/50 ,  C07K2319/70 ,  C12N2720/12322 ,  C12N2720/12334 ,  C12N2760/16022 ,  C12N2760/16034 ,  C12N2760/16134 ,  C12N2770/16022 ,  C12N2770/16034 ,  C12N2770/28122

    Abstract: Genes for proteins which spontaneously form dimers and/or oligomers can be recombinantly linked together, which upon expression in E. coli produces stable dimeric fusion proteins that spontaneously self-assemble into enormous, polyvalent complexes having increased immunogenicity and functionality. Linear, network and agglomerate complexes with enormous sizes and polyvalences are constructed using glutathione S-transferase, Norovirus P domains (NoV P− and NoV+), the protruding (P) domain of hepatitis E virus (HEV P), the astrovirus P domain (AstV), a monomeric peptide epitope (M2e of influenza virus), and/or a protein antigen (VP8* of rotavirus) fused in different combinations. The resulting complexes can contain hundreds to thousands NoV P-protein, HEV, AstV, M2e and/or VP8* copies and exhibit higher immunogenicity than the individual proteins alone. The large size and multivalent nature of the complexes are candidates as a bivalent or multivalent vaccines against Norovirus and other pathogens, and for generation of antibodies for diagnosis and research purposes.

    Abstract translation: 自发形成二聚体和/或寡聚体的蛋白质的基因可以重组连接在一起，其在大肠杆菌中表达后产生稳定的二聚融合蛋白，其自发地自组装成具有增加的免疫原性和功能性的巨大的多价复合物。 使用谷胱甘肽S-转移酶，诺如病毒P结构域（NoV P-和NoV +），戊型肝炎病毒（HEV P）的突出（P）结构域，星状病毒P结构域（...）构建具有巨大尺寸和多价性的线性，网络和聚集体复合物 AstV），单体肽表位（流感病毒的M2e）和/或以不同组合融合的蛋白质抗原（轮状病毒的VP8 *）。 所得复合物可以含有数百至数千个NoV P蛋白，HEV，AstV，M2e和/或VP8 *拷贝，并且比单独的蛋白质具有更高的免疫原性。 复合物的大尺寸和多价性质是针对诺如病毒和其他病原体的二价或多价疫苗的候选物，以及为诊断和研究目的产生抗体。

    Antigen-Norovirus P-domain monomers and dimers, antigen Norovirus P-particle molecules, and methods for their making and use
    5.
    发明授权
    Antigen-Norovirus P-domain monomers and dimers, antigen Norovirus P-particle molecules, and methods for their making and use 有权
    抗原诺如病毒P结构域单体和二聚体，抗原诺如病毒P颗粒分子及其制备和使用方法

    公开(公告)号：US09096644B2

    公开(公告)日：2015-08-04

    申请号：US13924906

    申请日：2013-06-24

    Applicant: Children's Hospital Medical Center

    Inventor： Ming Tan ,  Xi Jiang

    IPC: C07K7/06 ,  A61K38/00 ,  A61K39/12 ,  A61K39/125 ,  C07K5/10 ,  A61K39/00

    CPC classification number: C07K7/06 ,  A61K38/00 ,  A61K39/12 ,  A61K39/125 ,  A61K2039/5258 ,  A61K2039/542 ,  A61K2039/543 ,  A61K2039/55566 ,  A61K2039/58 ,  A61K2039/6075 ,  A61K2039/645 ,  A61K2039/70 ,  C07K5/10 ,  C12N2720/12334 ,  C12N2770/16034

    Abstract: A substituted Norovirus capsid protein monomer, having only the P-domain, includes a foreign antigen inserted into one or more of three surface loops present on each P-domain monomer by molecular cloning. The antigen-P-domain monomer can assemble spontaneously into an octahedral, antigen-Norovirus P-particle, composed of 24 copies of the monomer. Each substituted P-domain monomer can contain one to three copies of the foreign antigen, for a total of 24-72 antigen copies on each antigen-P-particle. The antigen-P-particle is useful in methods for diagnosing, immunizing and treating individuals infected with a foreign virus and as a carrier for development of vaccines against many infectious and non-infectious diseases. The substituted monomer can be readily produced in E. coli and yeast, are highly stable and tolerate a wide range of physio-chemical conditions. The P-particle-VP8 chimeras may also serve as a dual vaccine, for example, against both rotavirus and norovirus.

    Abstract translation: 仅具有P结构域的取代的诺如病毒衣壳蛋白单体包括通过分子克隆插入每个P-域单体上存在的三个表面环中的一个或多个的外源抗原。 抗原-P结构域单体可以自发组装成由24个单体组成的八面体抗原诺如病毒P颗粒。 每个取代的P-结构域单体可以含有一至三个拷贝的外源抗原，每个抗原-P-颗粒上共有24-72个抗原拷贝。 抗原-P颗粒可用于诊断，免疫和治疗感染外来病毒的个体的方法以及用于开发针对许多感染性和非感染性疾病的疫苗的载体。 取代的单体可以容易地在大肠杆菌和酵母中产生，高度稳定并且耐受广泛的生理化学条件。 P颗粒-PV8嵌合体也可以用作双重疫苗，例如针对轮状病毒和诺瓦病毒。

    HEMORRHAGIC FELINE CALICIVIRUS, CALICIVIRUS VACCINE AND METHOD FOR PREVENTING CALICIVIRUS INFECTION OR DISEASE
    10.
    发明申请
    HEMORRHAGIC FELINE CALICIVIRUS, CALICIVIRUS VACCINE AND METHOD FOR PREVENTING CALICIVIRUS INFECTION OR DISEASE 有权
    HEMORRHAGIC FELINE CALICIVIRUS，CALICIVIRUS VACCINE和预防CALICIVIRUS感染或疾病的方法

    公开(公告)号：US20110318383A1

    公开(公告)日：2011-12-29

    申请号：US13226685

    申请日：2011-09-07

    Applicant: Chengjin HUANG ,  Jennifer Hess

    Inventor： Chengjin HUANG ,  Jennifer Hess

    IPC: A61K39/295 ,  A61P31/12 ,  A61P37/04 ,  C12N7/00 ,  A61K39/125

    CPC classification number: C07K16/10 ,  A61K39/12 ,  A61K39/125 ,  A61K2039/552 ,  C12N7/00 ,  C12N2770/16034

    Abstract: The present invention relates to a novel, isolated and purified hemorrhagic feline calicivirus FCV-DD1. The invention further embraces monovalent and multivalent vaccines containing the new FCV-DD1 strain. In addition, the invention encompasses methods of protecting felines against infection or preventing disease caused by feline calicivirus alone or in addition to other pathogens that comprises administering to the felines an immunologically effective amount of the monovalent and multivalent vaccines described herein. Also, the invention concerns methods for diagnosing or detecting the hemorrhagic feline calicivirus in a susceptible host, asymptomatic carrier and the like by detecting the presence of feline calicivirus FCV-DD1 or antibodies raised or produced against feline calicivirus FCV-DDI antigen.

    Abstract translation: 本发明涉及一种新颖的分离纯化的出血性杯状病毒FCV-DD1。 本发明还包括含有新的FCV-DD1菌株的单价和多价疫苗。 此外，本发明包括保护猫科动物免受感染或预防单独的猫杯状病毒病引起的疾病或除了其它病原体之外的疾病的方法，其包括给予猫科动物免疫有效量的本文所述的单价和多价疫苗。 此外，本发明涉及通过检测猫杯状病毒FCV-DD1或针对猫杯状病毒FCV-DDI抗原产生或产生的抗体的存在来诊断或检测易感宿主中无出血性猫杯状病毒的方法，无症状载体等。

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