Nipah Virus Replicon Particles for Safe Immunization

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Solution Overview

Problem

There is currently no vaccine available for Nipah henipavirus (NiV), which is a highly pathogenic virus causing severe illness and death in humans and animals.

Innovation Solution

Development of NiV virus replicon particles (VRPs) that include a recombinant NiV genome with a deletion in the F protein gene, allowing for immune stimulation without producing infectious NiV particles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a live NiV vaccine is used to induce immune response, then immunogenicity is improved, but pathogenicity and safety are worsened

Engineering Contradiction:

ImproveimmunogenicityVSAvoidpathogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the harmful replication capability from the virus by deleting the F protein gene, which is essential for viral fusion and propagation. This leaves behind a replicon particle that can still present viral antigens (G and M proteins) to the immune system but cannot produce infectious particles, thus resolving the contradiction between immunogenicity and pathogenicity

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent creates a copy of the NiV genome that lacks the F protein coding sequence. This replicon particle serves as an immunogenic copy that mimics the structure and antigenicity of the wild-type virus without possessing the harmful replication and fusion functions, allowing safe induction of protective immunity

Inventive Principle:

Principle #26Copying

2Object-affected harmful factors

If a replicon particle with F protein deletion is used, then safety is improved, but ability to induce robust immune response is worsened

Engineering Contradiction:

ImprovesafetyVSAvoidimmune response induction

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent makes the replicon particle multi-functional by ensuring it expresses multiple viral proteins (G protein for attachment and M protein for membrane assembly) that are collectively sufficient to induce robust immune responses. The G protein provides strong antigenic stimulation while the M protein contributes to particle assembly and immunogenicity, compensating for the absent F protein function

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250064918A1Nipah henipavirus virus replicon particles and their use

Publication Date: 2025.02.27 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

Nipah henipavirus (NiV) virus replicon particles (VRPs) are disclosed herein. These VRPs can be used to induce an immune response to NiV or Hendra virus (HeV). In some embodiments, the NiV VRP include a recombinant NiV genome, wherein the recombinant NiV genome comprises a deletion in a nucleic acid sequence encoding the F protein such that functional mature F protein cannot be produced from the recombinant NiV genome; and a NiV envelope comprising F, G and M proteins of NiV. These VRP can infect human cells but cannot produce NiV particles from the infected human cells. Immunogenic compositions including the NiV VRP are also disclosed. In some embodiments, methods are disclosed for producing NiV VRP. The use of the disclosed NiV VRP to induce an immune response is also disclosed.