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Self-asssembling nanostructure vaccines

A nanostructure and vaccine technology, applied in nanotechnology, nanotechnology, nanomedicine, etc., can solve problems such as weak immune response

Pending Publication Date: 2020-12-15
UNIV OF WASHINGTON
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] A known limitation of subunit vaccines is that the immune response elicited may sometimes be weaker than that for other types of vaccines, such as whole virus, live vaccines, or live attenuated vaccines

Method used

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  • Self-asssembling nanostructure vaccines
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  • Self-asssembling nanostructure vaccines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0232] 9.1. Example 1: Respiratory syncytial virus (RSV)

[0233] 9.1.1. Sequence

[0234] In an embodiment of the present disclosure, the RSV F protein exists as a fusion protein with the first polypeptide and a linker is used, and the F protein-linker sequence may include the following:

[0235] >DS-Cav1-foldon (SEQ ID NO:90)

[0236](MELLILKANAITTILTAVTFCFASG)QNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIR(KSDELL) GYIPEAPRDGQAYVRKDGEWVLLSTFL

[0237] In various further embodiments, the first polypeptide comprises or consists of a first polypept...

Embodiment 2

[0326] 9.2. Example 2: Cytomegalovirus (CMV)

[0327]Protein-based vaccines for CMV are described, eg, in US Patent Publication Nos. US 2016 / 0159864A1 and US 2017 / 0369532A1; International Patent Publication No. WO 2016 / 092460A3; and Kirchmeier et al. Enveloped virus-like particle expression of human cytomegalovirus glycoprotein B antigen induces antibodies with potent and broadly neutralizing activity. Clin Vaccine Immunol. 2014;21(2):174–80. The homotrimeric complex of gB, the trimeric gH / gL / gO complex, or the pentameric gH / gL / pUL128 / pUL130 / pUL131A complex are considered three major targets for CMV vaccination.

[0328] The first of these targets, gB, forms a trimeric structure comprising several hydrophobic surfaces. The C-terminus of the extracellular domain of gB is proximal to the transmembrane region and is located near the 3-fold axis of the molecule. See Chandramouli et al. Structure of HCMV glycoprotein B in the postfusion conformation bound to aneutralizing human ...

Embodiment 3

[0331] 9.3. Example 3: Epstein-Barr Virus (EBV)

[0332] Epstein-Barr virus (EBV) represents a major global health concern. Although it is associated with infectious mononucleosis and an estimated 200,000 cases of cancer each year worldwide, there is no vaccine available. The main target of immunity is EBV glycoprotein 350 / 220 (gp350), which mediates attachment to B cells via complement receptor 2 (CR2 / CD21). See Kanekiyo et al. Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site. Cell 162(5):1090-1100 (2015). The extracellular domain of gp350 or the D of gp350 123 Fragments are expressed as gene fusions with nanostructured polypeptides, either as N-terminal or C-terminal fusions. The resulting gene fusions are expressed, assembled, and formulated into nanostructure-based vaccines. Antigenicity was determined using monoclonal antibodies 72A1 and 2L10.

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Abstract

The present disclosure provides nanostructures and nanostructure-based vaccines. Some nanostructures of the present disclosure display antigens capable of eliciting immune responses to infectious agents such as bacteria, viruses, and pathogens. Some vaccines of the present disclosure are useful for preventing or decreasing the severity of infection with an infectious agent, including, for exampleand without limitation, lyme disease, pertussis, herpes virus, orthomyxovirus, paramyxovirus, pneumovirus, filovirus, flavivirus, reovirus, retrovirus, meningococcus, or malaria. The antigens may be attached to the core of the nanostructure either non-covalently or covalently, including as a fusion protein or by other means disclosed herein. Multimeric antigens may optionally be displayed along asymmetry axis of the nanostructure. Also provided are proteins and nucleic acid molecules encoding such proteins, vaccine compositions, and methods of administration.

Description

[0001] cross reference [0002] This application claims priority to U.S. Provisional Patent Application Serial No. 62 / 636,757, filed February 28, 2018, and U.S. Provisional Patent Application Serial No. 62 / 724,721, filed August 30, 2018, each of which is incorporated by reference in its entirety into this article. [0003] Instructions for electronically submitting text files [0004] This application is electronically filed via EFS-Web and includes a sequence listing in .txt format for electronic submission. The .txt file contains a sequence listing named "ICVX_001_02WO_SeqList_ST25.txt" created on February 27, 2019 and is approximately 373 kilobytes in size. technical field [0005] The present disclosure relates generally to vaccines and methods of their use. In particular, the present disclosure relates to nanostructure-based vaccines capable of eliciting an immune response to antigens, such as antigenic proteins of various infectious agents, including bacteria, viruses...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/12B82Y40/00B82Y5/00
CPCB82Y5/00A61K39/12C12N2710/16134C12N2710/16234C12N2760/00034Y02A50/30A61P31/12C07K14/005A61K2039/6031C12N2760/18534C07K2319/00B82Y40/00C12N15/86
Inventor N·金D·贝克尔L·斯图尔特B·菲亚拉D·埃利斯L·卡特尔R·拉维钱德兰G·乌达J·法拉斯U·纳特曼
Owner UNIV OF WASHINGTON
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