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

公开(公告)号：ES2578979T3

公开(公告)日：2016-08-03

申请号：ES10841780

申请日：2010-12-31

Applicant: STC UNM

Inventor： PEABODY DAVID ,  CHACKERIAN BRYCE

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

Abstract: Una construcción (o constructo) de ácido nucleico que comprende: (a) un promotor bacteriano o bacteriofágico asociado operativamente con una secuencia de codificación para un dímero monocatenario de polipéptidos de recubrimiento de bacteriófagos de ARN, que comprende una secuencia primaria de codificación de polipéptidos de recubrimiento 'aguas arriba' ('upstream', en inglés) y una secuencia secundaria de codificación de polipéptidos de recubrimiento 'aguas abajo' ('downstream', en inglés), de manera que la secuencia de codificación de polipéptidos de recubrimiento 'aguas abajo' comprende un sitio para la inserción de una secuencia de codificación heteróloga; (b) un origen de replicación para la replicación en una procariota; (c) un gen con resistencia a los antibióticos; y (d) un codón de parada de traducción situado en la unión entre las secuencias de codificación de polipéptidos de recubrimiento 'aguas arriba' y 'aguas abajo'.

公开(公告)号：HK1174662A1

公开(公告)日：2013-06-14

申请号：HK13101590

申请日：2013-02-05

Applicant: STC UNM

Inventor： PEABODY DAVID ,  CHACKERIAN BRYCE

IPC: C12N20060101 ,  A61K20060101 ,  C07K20060101

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.

公开(公告)号：HK1203837A1

公开(公告)日：2015-11-06

申请号：HK15104584

申请日：2015-05-14

Applicant: STC UNM

Inventor： CHACKERIAN BRYCE ,  PEABODY DAVID ,  TUMBAN EBENEZER

IPC: A61K20060101 ,  A61P20060101 ,  C12N20060101

公开(公告)号：CA2861021A1

公开(公告)日：2013-07-18

申请号：CA2861021

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 in vivo.

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。