Epstein-Barr Virus-Like Particles Without Viral DNA

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Solution Overview

Problem

Current methods for developing a vaccine against Epstein-Barr virus (EBV) lack efficiency and safety, as existing vaccines do not prevent infection and can potentially induce virus replication or latent infection due to the presence of viral genomes in virus-like particles (VLPs).

Innovation Solution

The production of Epstein-Barr virus-like particles (EB-VLPs) substantially free of EBV DNA, achieved by modifying the EBV genome to lack essential genes and using a suitable host cell to generate VLPs without viral replication or latent infection, ensuring the VLPs are empty and devoid of DNA, thereby enhancing safety and efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional VLP production methods are used, then VLPs are produced, but viral genomes (DNA or RNA) are present in the VLPs, which can induce virus replication and latent infection

Engineering Contradiction:
Improvesafety of vaccineVSAvoidvirus replication and latent infection
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and removes the viral genome (DNA or RNA) from the virus-like particles while retaining the VLP structure. This is achieved by using mutant viruses that cannot package their genome into VLPs, thereby producing VLPs that are free of viral genetic material and cannot induce replication or latent infection.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention converts the harmful presence of viral genomes in VLPs into a benefit by deliberately using mutant viruses with defective genome packaging capabilities. These mutants, which would normally be considered defective or harmful, are instead utilized to produce safe VLPs that cannot replicate but maintain immunogenicity.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

2Reliability

If peptidic vaccines are used, then they are safe, but they do not prevent EBV infection effectively

Engineering Contradiction:
Improvesafety of vaccineVSAvoidefficacy in preventing infection
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The invention creates a composite vaccine structure by combining the safety of peptide-based approaches with the enhanced immunogenicity of VLPs. The resulting EBV-VLPs incorporate viral structural proteins that self-assemble into particle forms, providing both the safety profile needed for vaccination and the structural complexity required to elicit strong protective immune responses.

Inventive Principle:
Principle #40Composite materials

3Productivity

If VLPs containing viral genomes are used, then they can stimulate immune response, but they risk inducing virus replication and latent infection

Engineering Contradiction:
Improveimmunogenic propertiesVSAvoidrisk of infection
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and removes the viral genome (DNA or RNA) from the virus-like particles while retaining the VLP structure. This is achieved by using mutant viruses that cannot package their genome into VLPs, thereby producing VLPs that are free of viral genetic material and cannot induce replication or latent infection.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention creates accurate copies of the viral particle structure (VLPs) without including the harmful viral genome. These VLP copies mimic the native virus morphology and surface proteins, enabling them to stimulate the immune system effectively while lacking the genetic material necessary for replication and infection.

Inventive Principle:
Principle #26Copying

Data Source

PatentEP2797626B1Second generation virus-like particles (VLP) from epstein-barr viruses for vaccination purposes
Publication Date: 2019.07.03 DEUTES KREBSFORSCHUNGSZENT STIFTUNG DES OFFENTLICHEN RECHTS
  • EP2797626B1 patent drawingFigure 1
  • EP2797626B1 patent drawingFigure 2
  • EP2797626B1 patent drawingFigure 3

AI summary

The present invention relates to an Epstein-Barr virus-like particle (EB-VLP) substantially free of Epstein-Barr Virus (EBV) DNA. The present invention also relates to a polynucleotide comprising an EBV genome a) lacking at least one expressible gene selected from the group consisting of the BFLF1 gene, the BBRF gene, the BGRF1 gene, the BDRF1 gene, the BALF3 gene, the BFRF1A gene, and the BFRF1 gene, and b) producing the EB-VLP of the invention in a suitable host cell. The present invention further relates to a vector and a host cell comprising the polynucleotide of the invention as well to a method of manufacturing said EB-VLPs, a method of manufacturing a vaccine thereof, a vaccine and a composition comprising said EB-VLPs.