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    IMMUNOGENIC HPV L2-CONTAINING VLPS AND RELATED COMPOSITIONS AND METHODS
    3.
    发明授权
    IMMUNOGENIC HPV L2-CONTAINING VLPS AND RELATED COMPOSITIONS AND METHODS 有权
    免疫原性含HPV L2的VLPS及相关组合物和方法

    公开(公告)号：EP2802349B1

    公开(公告)日：2017-12-06

    申请号：EP13736349.5

    申请日：2013-01-10

    Applicant: STC.UNM

    Inventor： CHACKERIAN, Bryce ,  PEABODY, David ,  TUMBAN, Ebenezer

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

    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.

    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
    RNA噬菌体类病毒粒子的多肽筛选及亲和力筛选方法

    公开(公告)号：WO2011082381A2

    公开(公告)日：2011-07-07

    申请号：PCT/US2010/062638

    申请日：2010-12-31

    Applicant: STC.UNM ,  PEABODY, David, S. ,  CHACKERIAN, Bryce

    Inventor： PEABODY, David, S. ,  CHACKERIAN, Bryce

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

    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: 本发明涉及用于控制病毒样颗粒（VLP）上肽显示效价的系统和方法，特别是包括MS2 VLP。 在这种方法中，大量的野生型和低量的单链二聚体外壳蛋白可以由单一RNA产生。 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，允许在VLP上显示效价水平的轻松调整，从而控制了Valence的免疫原（疫苗）生产，特别是 MS2 VLPS在很宽的范围内，从平均不到一个 - 到每个粒子多达九十个。 这有助于免疫原和疫苗的生产，包括低价价的VLP。 公开了用于表达病毒样颗粒的核酸构建体，其包含通过插入异源肽而修饰的MS2的外壳多肽，其中异源肽显示在病毒样颗粒上并包裹MS2 mRNA。 还公开了核酸构建体，其可用于表达由插入异源肽修饰的PP7外壳多肽组成的病毒样颗粒，其中异源肽显示在病毒样颗粒上并包裹PP7 mRNA。 / p>

    PLASMIDS AND METHODS FOR PEPTIDE DISPLAY AND AFFINITY-SELECTION ON VIRUS-LIKE PARTICLES OF RNA BACTERIOPHAGES
    6.
    发明申请
    PLASMIDS AND METHODS FOR PEPTIDE DISPLAY AND AFFINITY-SELECTION ON VIRUS-LIKE PARTICLES OF RNA BACTERIOPHAGES 审中-公开

    公开(公告)号：WO2013003353A3

    公开(公告)日：2013-01-03

    申请号：PCT/US2012/044206

    申请日：2012-06-26

    Applicant: STC.UNM ,  PEABODY, David, S. ,  CHACKERIAN, Bryce

    Inventor： PEABODY, David, S. ,  CHACKERIAN, Bryce

    IPC: C12N7/01 ,  C12N15/86 ,  A61K39/12

    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.

    IMMUNOGENIC HPV L2-CONTAINING VLPS AND RELATED COMPOSITIONS AND METHODS
    8.
    发明公开
    IMMUNOGENIC HPV L2-CONTAINING VLPS AND RELATED COMPOSITIONS AND METHODS 有权
    免疫原性HPV病毒样颗粒L2基于和相关组合物和方法

    公开(公告)号：EP2802349A1

    公开(公告)日：2014-11-19

    申请号：EP13736349.5

    申请日：2013-01-10

    Applicant: STC.UNM

    Inventor： CHACKERIAN, Bryce ,  PEABODY, David ,  TUMBAN, Ebenezer

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

    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.

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