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    A VIRUS-LIKE PLATFORM FOR RAPID VACCINE DISCOVERY
    1.
    发明申请
    A VIRUS-LIKE PLATFORM FOR RAPID VACCINE DISCOVERY 审中-公开
    一种用于快速疫苗发现的病毒式平台

    公开(公告)号：WO2008024427A3

    公开(公告)日：2008-04-17

    申请号：PCT/US2007018614

    申请日：2007-08-23

    Applicant: STC UNM ,  PEABODY DAVID S ,  CHACKERIAN BRYCE

    Inventor： PEABODY DAVID S ,  CHACKERIAN BRYCE

    IPC: A61K48/00 ,  A61K39/12

    CPC classification number: C12N15/1037 ,  A61K2039/5256 ,  A61K2039/5258 ,  C07K14/005 ,  C12N2740/16122 ,  C12N2795/18123 ,  C40B40/02

    Abstract: The invention is directed to virus-like particles (VLPs)of an RNA bacteriophage that (a) comprises a coat polypeptide of said phage modified by insertion of a heterologous peptide that is displayed on said VLP and (b) encapsidates said bacteriophage mRNA as well as populations of these VLPs, and their uses. The invention is further directed to VLPs that encapsidate heterologous substances, as well as populations of these VLPs and their uses.

    Abstract translation: 本发明涉及RNA噬菌体的病毒样颗粒（VLP），其（a）包含通过插入在所述VLP上显示的异源肽修饰的所述噬菌体的外壳多肽，和（b）还包封所述噬菌体mRNA 作为这些VLP的群体及其用途。 本发明还涉及包裹异源物质的VLP以及这些VLP的群体及其用途。

    PLASMIDS AND METHODS FOR PEPTIDE DISPLAY AND AFFINITY-SELECTION ON VIRUS-LIKE PARTICLES OF RNA BACTERIOPHAGES
    3.
    发明申请
    PLASMIDS AND METHODS FOR PEPTIDE DISPLAY AND AFFINITY-SELECTION ON VIRUS-LIKE PARTICLES OF RNA BACTERIOPHAGES 审中-公开
    肽类显示的方法和方法及RNA病毒类病毒颗粒的选择

    公开(公告)号：WO2013003353A2

    公开(公告)日：2013-01-03

    申请号：PCT/US2012044206

    申请日：2012-06-26

    Applicant: STC UNM ,  PEABODY DAVID S ,  CHACKERIAN BRYCE

    Inventor： PEABODY DAVID S ,  CHACKERIAN BRYCE

    CPC classification number: C07K14/005 ,  A61K39/00 ,  A61K2039/5256 ,  A61K2039/5258 ,  C07K2319/40 ,  C07K2319/735 ,  C12N2795/18122 ,  C12N2795/18123

    Abstract: The present invention relates to a system and method for controlling peptide display valency on virus-like particles (VLPs), especially including MS2 or PP7 VLPs. In this method, large amounts of wild-type and low quantities of single-chain dimer coat proteins may be produced from a single RNA. Valency is controlled in immunogen (vaccine) production by providing a system that allows the production of large amounts of wild-type and low quantities of single-chain dimer coating proteins from a single RNA, allowing facile adjustment of display valency levels on bacteriophage VLPs, especially MS2 or PP7 VLPs over a wide range, from few than one- on average- to as many as ninety per particle. This facilitates the production of immunogens and vaccines, including VLPs exhibiting low valency. Nucleic acid constructs useful in the expression of virus-like particles are disclosed, comprised of a coat polypeptide of bacteriophage such as MS2 or PP7 modified by insertion of a heterologous peptide, optionally comprising a carbohydrate mimotope, wherein the heterologous peptide is displayed on the virus-like particle and encapsidates bacteriphage mRNA.

    Abstract translation: 本发明涉及一种用于控制病毒样颗粒（VLPs），特别是包括MS2或PP7VLP的肽展示剂价态的系统和方法。 在该方法中，可以从单个RNA产生大量野生型和低量的单链二聚体外壳蛋白。 通过提供允许从单个RNA产生大量野生型和少量单链二聚体包被蛋白的系统，允许容易地调节噬菌体VLP上的显示价态水平，从而在免疫原（疫苗）生产中控制价值， 特别是广泛范围的MS2或PP7 VLP，从一个平均至少一个到每个颗粒的九十个。 这有助于免疫原和疫苗的生产，包括显示低效价的VLP。 公开了可用于病毒样颗粒表达的核酸构建体，其包括噬菌体的外壳多肽，例如通过插入异源肽修饰的MS2或PP7，任选地包含碳水化合物模拟表位，其中异源肽显示在病毒上 样颗粒并包裹细菌噬菌体mRNA。

    PLASMIDS AND METHODS FOR PEPTIDE DISPLAY AND AFFINITY-SELECTION ON VIRUS-LIKE PARTICLES OF RNA BACTERIOPHAGES
    4.
    发明申请
    PLASMIDS AND METHODS FOR PEPTIDE DISPLAY AND AFFINITY-SELECTION ON VIRUS-LIKE PARTICLES OF RNA BACTERIOPHAGES 审中-公开
    用于肽显示的方法和方法以及RNA嗜酸性粒细胞样病毒颗粒的选择

    公开(公告)号：WO2011082381A3

    公开(公告)日：2011-12-22

    申请号：PCT/US2010062638

    申请日：2010-12-31

    Applicant: STC UNM ,  PEABODY DAVID S ,  CHACKERIAN BRYCE

    Inventor： PEABODY DAVID S ,  CHACKERIAN BRYCE

    IPC: C12N7/01 ,  A61K39/12 ,  C07K14/005 ,  C12N15/33

    CPC classification number: A61K39/12 ,  A61K39/07 ,  A61K2039/5256 ,  A61K2039/5258 ,  C12N7/00 ,  C12N15/1037 ,  C12N2710/20022 ,  C12N2710/20034 ,  C12N2740/16034 ,  C12N2740/16134 ,  C12N2795/16021 ,  C12N2795/16022 ,  C12N2795/16023 ,  C12N2795/16042 ,  C12N2795/18023 ,  C40B40/08

    Abstract: The present invention relates to a system and method for controlling peptide display valency on virus-like particles (VLPs), especially including MS2 VLPs. In this method, large amounts of wild-type and low quantities of single-chain dimer coat proteins may be produced from a single RNA. Valency is controlled in immunogen (vaccine) production by providing a system that allows the production of large amounts of wild-type and low quantities of single-chain dimer coating proteins from a single RNA, allowing facile adjustment of display valency levels on VLPs, especially MS2 VLPS over a wide range, from few than one- on average- to as many as ninety per particle. This facilitates the production of immunogens and vaccines, including VLPs exhibiting low valency. Nucleic acid constructs useful in the expression of virus-like particles are disclosed, comprised of a coat polypeptide of MS2 modified by insertion of a heterologous peptide, wherein the heterologous peptide is displayed on the virus-like particle and encapsidates MS2 niRNA. Nucleic acid constructs are also disclosed which are useful in the expression of virus-like particles comprised of a coat polypeptide of PP7 modified by insertion of a heterologous peptide, wherein the heterologous peptide is displayed on the virus-like particle and encapsidates PP7 mRNA.

    Abstract translation: 本发明涉及一种用于控制病毒样颗粒（VLP）的肽显示价态的系统和方法，特别是包括MS2 VLP。 在该方法中，可以从单个RNA产生大量野生型和低量的单链二聚体外壳蛋白。 通过提供允许从单个RNA生产大量野生型和少量单链二聚体包被蛋白质的系统，允许容易调整VLP上的显示剂价位水平，特别是在免疫原（疫苗）生产中控制价值 MS2 VLPS在广泛的范围内，从一个平均至少一个到每个颗粒多达九十个。 这有助于免疫原和疫苗的生产，包括显示低价的VLP。 公开了可用于病毒样颗粒表达的核酸构建体，其由通过插入异源肽修饰的MS2的外壳多肽组成，其中异源肽显示在病毒样颗粒上并包裹MS2nRNA。 还公开了核酸构建体，其可用于表达由通过插入异源肽修饰的PP7的外壳多肽组成的病毒样颗粒的表达，其中异源肽显示在病毒样颗粒上并包裹PP7 mRNA。

    METHODS FOR SCREENING VIRAL LIKE PARTICLES AND IDENTIFYING NEUTRALIZING EPITOPES AND RELATED VACCINES, CONSTRUCTS, AND LIBRARIES
    5.
    发明申请
    METHODS FOR SCREENING VIRAL LIKE PARTICLES AND IDENTIFYING NEUTRALIZING EPITOPES AND RELATED VACCINES, CONSTRUCTS, AND LIBRARIES 审中-公开
    筛选病毒颗粒和识别中性疱疹病毒和相关疫苗，构造和图像的方法

    公开(公告)号：WO2013063366A3

    公开(公告)日：2013-07-11

    申请号：PCT/US2012062073

    申请日：2012-10-26

    Applicant: STC UNM

    Inventor： HJELLE BRIAN L ,  PEABODY DAVID S ,  CHACKERIAN BRYCE

    IPC: G01N33/68 ,  C12Q1/68 ,  G01N33/569

    CPC classification number: G01N33/6878 ,  G01N33/56983 ,  G01N33/6845

    Abstract: The invention is directed to methods of screening immunogenic viral like particles and related immunogenic compositions and diagnostic techniques. In one embodiment, the invention provides methods of screening immunogenic viral like particles containing peptides corresponding to epitope regions of a wide variety of pathogens, including viruses, bacteria, parasites, and microbes. Non-infectious antigens and allergens of interest can also be screened as described herein. Immunization, therapeutic and diagnostic applications are also described for the compositions and methods according to the invention. In another embodiment, the invention provides novel methods of identifying a cryptic neutralizing epitope and related vaccines, constructs, and libraries. In some embodiments, these methods use high-throughput formats that are facilitated by in silica or in vitro steps.

    Abstract translation: 本发明涉及筛选免疫原性病毒样颗粒和相关的免疫原性组合物和诊断技术的方法。 在一个实施方案中，本发明提供筛选含有对应于多种病原体（包括病毒，细菌，寄生虫和微生物）的表位区域的肽的免疫原性病毒样颗粒的方法。 还可以如本文所述筛选感兴趣的非传染性抗原和过敏原。 还描述了根据本发明的组合物和方法的免疫，治疗和诊断应用。 在另一个实施方案中，本发明提供鉴定隐性中和表位和相关疫苗，构建体和文库的新方法。 在一些实施方案中，这些方法使用通过二氧化硅或体外步骤促进的高通量形式。

    IMMUNOGENIC HPV L2-CONTAINING VLPS AND RELATED COMPOSITIONS, CONSTRUCTS, AND THERAPEUTIC METHODS
    7.
    发明申请
    IMMUNOGENIC HPV L2-CONTAINING VLPS AND RELATED COMPOSITIONS, CONSTRUCTS, AND THERAPEUTIC METHODS 审中-公开
    免疫原性HPV L2含有VLPS及相关组合物，构造和治疗方法

    公开(公告)号：WO2011100234A3

    公开(公告)日：2012-03-15

    申请号：PCT/US2011024030

    申请日：2011-02-08

    Applicant: STC UNM ,  CHACKERIAN BRYCE ,  PEABODY DAVID S

    Inventor： CHACKERIAN BRYCE ,  PEABODY DAVID S

    IPC: A61K38/17 ,  A61K38/16 ,  A61K47/30 ,  A61K47/48 ,  A61P31/00 ,  A61P31/12

    CPC classification number: C07K14/005 ,  A61K39/12 ,  A61K47/48776 ,  A61K47/6901 ,  A61K2039/5258 ,  A61K2039/55566 ,  C12N7/00 ,  C12N2710/20023 ,  C12N2710/20034 ,  C12N2795/18123

    Abstract: The invention provides immunotherapeutic and prophylactic bacteriophage viral-like particle (VLPs) which are useful in the treatment and prevention of human papillomavirus (HPV) infections and related disorders, including cervical cancer and persistent infections associated with HPV. Related compositions (e.g. vaccines), nucleic acid constructs, and therapeutic methods are also provided. VLPsand related ompositions of the invention induce high titer antibody responses against HPV L2 and protect against HPV challenge in vivo. VLPs, VLP-containing compositions, and therapeutic methods of the invention induce an immunogenic response against HPV infection, confer immunity against HPV infection, protect against HPV infection, and reduce the likelihood of infection by HPV infection.

    Abstract translation: 本发明提供免疫治疗和预防性噬菌体病毒样颗粒（VLP），其可用于治疗和预防人乳头状瘤病毒（HPV）感染和相关疾病，包括宫颈癌和与HPV相关的持续感染。 还提供了相关组合物（例如疫苗），核酸构建体和治疗方法。 本发明的VLPs和相关症状诱导针对HPV L2的高滴度抗体应答并且在体内保护免受HPV挑战。 VLP，含VLP的组合物和本发明的治疗方法诱导针对HPV感染的免疫原性应答，赋予HPV感染免疫，防止HPV感染，并降低HPV感染感染的可能性。

    Immunogenic HPV L2-containing VLPs and related compositions and methods
    8.
    发明专利
    Immunogenic HPV L2-containing VLPs and related compositions and methods 未知

    公开(公告)号：AU2013207962A1

    公开(公告)日：2014-08-07

    申请号：AU2013207962

    申请日：2013-01-10

    Applicant: STC UNM

    Inventor： CHACKERIAN BRYCE ,  PEABODY DAVID ,  TUMBAN EBENEZER

    IPC: A61K39/12 ,  A61P31/20 ,  C12N7/01

    Abstract: In one aspect, the invention provides immunogenic HPV L2-containing viral-like particles (VLPs). Related compositions (e.g. vaccines), nucleic acid constructs, and therapeutic methods are also provided. In certain aspects, the VLPs are comprised of a coat polypeptide of the bacteriophages PP7 or MS2, wherein the coat protein is modified by insertion of peptide antigens derived from HPV L2, and wherein the HPV L2 peptide is displayed on the VLP and encapsidates PP7 or MS2 mRNA. Specifically, VLPs of the invention display L2 peptides at the N- terminus of the bacteriophage coat protein. Surprisingly, these L2-displaying VLPs induce more broadly neutralizing antibody responses than when the same peptide is displayed in the AB-loop such that the immunogenic response is enhanced by a factor of at least 10. Immunogenic VLPs and related compositions of the invention induce high titer antibody responses against HPV L2 and protect against HPV challenge

    IMMUNOGENIC HPV L2-CONTAINING VLPS AND RELATED COMPOSITIONS AND METHODS
    10.
    发明公开
    IMMUNOGENIC HPV L2-CONTAINING VLPS AND RELATED COMPOSITIONS AND METHODS 有权
    免疫缺陷型HPV L2-HALTIGE VLPS UND VERWANDTE ZUSAMMENSETZUNGEN UND VERFAHREN

    公开(公告)号：EP2802349A4

    公开(公告)日：2015-08-26

    申请号：EP13736349

    申请日：2013-01-10

    Applicant: STC UNM

    Inventor： CHACKERIAN BRYCE ,  PEABODY DAVID ,  TUMBAN EBENEZER

    IPC: A61K39/12 ,  A61P31/20 ,  C12N7/01

    CPC classification number: A61K39/12 ,  A61K2039/5258 ,  A61K2039/58 ,  C12N2710/20034 ,  C12N2795/18142 ,  C12N2795/18143

    Abstract: In one aspect, the invention provides immunogenic HPV L2-containing viral-like particles (VLPs). Related compositions (e.g. vaccines), nucleic acid constructs, and therapeutic methods are also provided. In certain aspects, the VLPs are comprised of a coat polypeptide of the bacteriophages PP7 or MS2, wherein the coat protein is modified by insertion of peptide antigens derived from HPV L2, and wherein the HPV L2 peptide is displayed on the VLP and encapsidates PP7 or MS2 mRNA. Specifically, VLPs of the invention display L2 peptides at the N- terminus of the bacteriophage coat protein. Surprisingly, these L2-displaying VLPs induce more broadly neutralizing antibody responses than when the same peptide is displayed in the AB-loop such that the immunogenic response is enhanced by a factor of at least 10. Immunogenic VLPs and related compositions of the invention induce high titer antibody responses against HPV L2 and protect against HPV challenge in vivo.

    Abstract translation: 一方面，本发明提供了含免疫原性的含有HPV L2的病毒样颗粒（VLP）。 还提供了相关组合物（例如疫苗），核酸构建体和治疗方法。 在某些方面，VLP由噬菌体PP7或MS2的外壳多肽组成，其中通过插入衍生自HPV L2的肽抗原修饰外壳蛋白，并且其中HPV L2肽显示在VLP上并且包裹PP7或 MS2 mRNA。 具体地，本发明的VLP在噬菌体外壳蛋白的N-末端显示L2肽。 令人惊讶的是，这些L2显示的VLP诱导比在AB环中显示相同的肽更广泛的中和抗体应答，使得免疫原性应答增加至少10倍。本发明的免疫原性VLP和相关组合物诱导高 针对HPV L2的滴度抗体应答和在体内防止HPV挑战。

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