Title:
PREFUSION STABILIZED EBV GB MUTATIONS AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO/2024/006930
Kind Code:
A3
Abstract:
We have generated a 3D model of the glycoprotein B (gB) of Epstein-Barr virus (EBV) to design candidate stabilizing mutations that increase the stability of the prefusion state essential for an effective EBV gB based vaccine. Provided herein are engineered polypeptides derived from the EBV gB, which include an altered EBV gB ectodomain that has modifications relative to the native EBV gB ectodomain that stabilize a prefusion conformation of the polypeptides. In various aspects, the modifications are amino acid substitutions to generate pairs of cysteine amino acid residues, preferably positioned to connect different domains of the polypeptide or different copies of the polypeptide in a trimeric or multimeric conformation via formation of disulfide bonds during protein expression. In additional aspects, the modifications and/or the engineered polypeptides do not contain pairs of cysteine amino acid residues that may form disulfide bonds in a postfusion conformation.
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Inventors:
PRICE JASON (US)
HARO BIANKA (US)
RUFF RAYMOND (US)
OLSON JIM (US)
HARO BIANKA (US)
RUFF RAYMOND (US)
OLSON JIM (US)
Application Number:
PCT/US2023/069411
Publication Date:
April 04, 2024
Filing Date:
June 29, 2023
Export Citation:
Assignee:
SEATTLE CHILDRENS HOSPITAL DBA SEATTLE CHILDRENS RES INST (US)
International Classes:
A61K39/12; A61K39/245; A61P31/22; A61K38/16; A61P37/04
Other References:
BACKOVIC ET AL.: "Structure of a trimeric variant of the Epstein-Barr virus glycoprotein B", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 106, no. 8, February 2009 (2009-02-01), pages 2880 - 5, XP055372474, DOI: 10.1073/pnas.0810530106
JESSICA J. REIMER, MARIJA BACKOVIC, CHARUHAS G DESHPANDE, THEODORE JARDETZKY, RICHARD LONGNECKER: "Analysis of Epstein-Barr Virus Glycoprotein B Functional Domains via Linker Insertion Mutagenesis", JOURNAL OF VIROLOGY, THE AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 83, no. 2, 15 January 2009 (2009-01-15), US , pages 734 - 747, XP093158400, ISSN: 0022-538X, DOI: 10.1128/JVI.01817-08
PLATE ET AL.: "Mapping regions of Epstein-Barr virus (EBV) glycoprotein B (gB) important for. fusion function with gH/gL", VIROLOGY, vol. 413, no. 1, April 2011 (2011-04-01), pages 26 - 38, XP028159145, DOI: 10.1016/j.virol.2010.12.006
JESSICA J. REIMER, MARIJA BACKOVIC, CHARUHAS G DESHPANDE, THEODORE JARDETZKY, RICHARD LONGNECKER: "Analysis of Epstein-Barr Virus Glycoprotein B Functional Domains via Linker Insertion Mutagenesis", JOURNAL OF VIROLOGY, THE AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 83, no. 2, 15 January 2009 (2009-01-15), US , pages 734 - 747, XP093158400, ISSN: 0022-538X, DOI: 10.1128/JVI.01817-08
PLATE ET AL.: "Mapping regions of Epstein-Barr virus (EBV) glycoprotein B (gB) important for. fusion function with gH/gL", VIROLOGY, vol. 413, no. 1, April 2011 (2011-04-01), pages 26 - 38, XP028159145, DOI: 10.1016/j.virol.2010.12.006
Attorney, Agent or Firm:
ZHU, Suwei et al. (US)
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