HEV VLP Antigen Delivery Mucosal Immunity

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Solution Overview

Problem

Current vaccine delivery methods face challenges in effectively targeting mucosal tissues and inducing immune responses through oral administration, particularly for hepatitis E virus (HEV), where existing technologies struggle to provide broad and efficacious immunity.

Innovation Solution

A composition comprising a modified hepatitis E virus (HEV) capsid protein and a heterologous nucleic acid encapsulated in a chimeric virus-like particle (VLP) is developed, allowing for the delivery of both peptide and nucleic acid antigens to mucosal tissues, utilizing the HEV VLP's ability to self-assemble and reassemble, and its stability at room temperature.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional vaccine delivery methods are used, then vaccination can be administered, but effective targeting of mucosal tissues and induction of immune responses through oral administration is achieved poorly

Engineering Contradiction:

Improveimmune response inductionVSAvoidoral administration effectiveness

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent employs HEV VLPs as intermediary carriers that mediate the delivery of antigens to mucosal tissues. The VLPs serve as a bridge between the administered vaccine and the target mucosal immune system, enabling effective oral administration by exploiting the natural tropism of HEV VLPs for mucosal surfaces and intestinal epithelium.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The HEV VLP platform is designed to perform multiple functions simultaneously: it acts as a delivery vehicle for both peptide and nucleic acid antigens, provides structural stability, induces immunogenicity, and targets mucosal tissues. This multi-functionality resolves the contradiction by consolidating multiple vaccine requirements into a single effective platform.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If heterologous nucleic acid and peptide are combined in VLP, then broad and efficacious immunity is achieved, but VLP structure and assembly complexity increases

Engineering Contradiction:

Improveantigen delivery capabilityVSAvoidVLP structure

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent segments the antigen delivery function into distinct components: the HEV VLP provides the structural framework and delivery capability, while separate peptide and nucleic acid antigens are incorporated as cargo. This segmentation allows each component to be optimized independently while maintaining overall system versatility.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The VLP structure employs a nested arrangement where the heterologous nucleic acid is encapsulated within the VLP core, and heterologous peptides are displayed on the surface. This nesting strategy accommodates multiple antigen types within a single particle structure without proportionally increasing overall complexity.

Inventive Principle:

Principle #7Nested doll (Nesting)

3Ease of operation

If HEV VLP is used for oral administration, then mucosal tissue delivery is improved, but stability at room temperature and resistance to environmental factors is reduced

Engineering Contradiction:

Improvemucosal deliveryVSAvoidroom temperature stability

Core Design Contradiction:

Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent modifies parameters of the VLP structure through chimeric construction with heterologous proteins and peptides, which alters the stability characteristics while preserving mucosal delivery capability. These parameter changes in protein composition and structure enable enhanced environmental stability without sacrificing the key mucosal tropism function.

Inventive Principle:

Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The modified HEV VLP system induces significant humoral and cellular immune responses, including specific IgM, IgG, and IgA antibodies, as well as CTL responses, effectively delivering antigens to mucosal tissues and providing broad protection against HEV and other pathogens like HIV, demonstrating enhanced immunogenicity and stability.

Implementation Method 1

When expressed in insect Tn5 cells, the truncated capsid protein (CP) covering residues 112-608 is able to self-assemble into virus-like particle (VLP)

Methodology Applied

Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

this HEV chimeric VLP is able to stimulate humoral immune response and significant level of IgM and IgG antibodies to the inserted epitope and HEV were observed in intestinal secretions

Methodology Applied

Scientific EffectHumoral immune response:

Implementation Method 3

mice used in the study exhibited CTL response specific to gp120 in the spleen, Payer's patches and mesenteric lymph modes

Methodology Applied

Scientific EffectCellular immune response:

Implementation Method 4

the HEV VLP can disassemble and reassemble in vitro with the ability of encapsidating DNA plasmids

Methodology Applied

Scientific EffectDisassembly and reassembly:

Data Source

PatentUS8906862B2Multiple antigen delivery system using hepatitis E virus-like particle

Publication Date: 2014.12.09 RGT UNIV OF CALIFORNIA

AI summary

This invention provides a peptide/nucleic acid composition for oral/mucosal, dual-modal activation of immune protection systems.