Measles Virus DI Particle Composition for Stronger IFN Signaling

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Solution Overview

Problem

Existing measles virus (MV) vaccines and recombinant MV-based vaccines do not efficiently produce defective interfering (DI) genomes in vivo, which are crucial for inducing a strong type-I interferon response and immunostimulatory activity, limiting their effectiveness as vaccine vectors for heterologous antigens.

Innovation Solution

A composition comprising a mixture of infectious replicating viral particles and DI particles of recombinant MV-derived viruses, with DI genomes representing a significant percentage of the full-length MV genomic RNA, is developed to enhance immunostimulatory activity and type-I interferon signaling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If standard live attenuated measles virus vaccines are used, then the vaccine is easy to manufacture and administer, but the production of defective interfering (DI) genomes is insufficient, limiting immunostimulatory activity

Engineering Contradiction:

Improvevaccine productionVSAvoidimmunostimulatory activity

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent modifies the measles virus vaccine strain by introducing specific genetic modifications that enhance DI genome production. The modified virus maintains replicative capability while producing significantly higher levels of DI genomes, thereby improving immunostimulatory activity without compromising manufacturability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses defective interfering genomes as intermediaries to enhance the immunostimulatory effect. These DI genomes act as molecular adjuvants that stimulate type-I interferon production and innate immune signaling, bridging the gap between simple vaccination and enhanced immune activation

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If recombinant MV-based vaccines are used to deliver heterologous antigens, then vaccine versatility is improved, but DI genome production efficiency decreases, reducing adjuvant effect

Engineering Contradiction:

Improvevaccine vector capabilityVSAvoidDI genome production

Core Design Contradiction:

Adaptability or versatilityVSProductivity

Solution Approach 1:

The patent segments the vaccine function into two components: the recombinant measles virus vector that delivers heterologous antigens, and the enhanced DI genome production that provides adjuvant activity. This segmentation allows the vaccine to maintain versatility while restoring DI genome production through specific genetic modifications of the vector

Inventive Principle:

Principle #1Segmentation

3Device complexity

If conventional measles virus vaccines are used, then manufacturing complexity is low, but type-I interferon response induction is weak, limiting immune response strength

Engineering Contradiction:

Improvevaccine formulationVSAvoidimmune response

Core Design Contradiction:

Device complexityVSStrength

Solution Approach 1:

The patent introduces defective interfering genomes as intermediary molecules that specifically trigger type-I interferon production through recognition by cytosolic RIG-I-like receptors. This intermediary mechanism amplifies the immune response without requiring complex vaccine formulations or additional adjuvant components

Inventive Principle:

Principle #24Intermediary (Mediator)

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 composition effectively stimulates a robust immune response by enhancing DI genome production, providing a potent adjuvant effect and improved immunogenicity for vectored antigens, such as those from arboviruses and parasites like Chikungunya virus and Plasmodium falciparum.

Implementation Method 1

5′ copy-back DI genomes have been described as pathogen-associated molecular patterns (PAMPs) for RIG-I (11-13) and MDA5 (12). These RNA molecules activate innate signalling through cytosolic RIG-I-like receptors (RLRs).

Methodology Applied

Scientific EffectRIG-I-like receptor recognition:

Implementation Method 2

RIG-I-dependent IFN-β signalling mediated by 5′copy-back DI genome is enhanced in the presence of Interferon-inducible double-stranded RNA-dependent protein kinase activator A (PACT) that also binds the DI RNA.

Methodology Applied

Scientific EffectProtein-RNA binding:

Implementation Method 3

Additionally, accumulation of DI-RNAs is the trigger for double-stranded RNA-dependent protein kinase (PKR) activation that generates a cellular stress response, resulting in translational arrest and formation of stress granules.

Methodology Applied

Scientific EffectPKR activation by dsRNA:

Data Source

PatentUS12533404B2Compositions and methods comprising measles virus defective interfering particles for the prevention of infectious diseases

Publication Date: 2026.01.27 MINIST DES ARMEES DIRECTION CENT DU SERVICE DE SANTE DES ARMEES

AI summary

The invention is in the field of prevention or treatment of diseases, in particular infectious diseases, and more particularly in the field of multivalent vaccines. The inventors characterized 5′ copy-back DI-RNAs produced by recombinant MV strains, including rMV-based vaccines and wild-type MV (wt-MV). The efficiency of these DI-RNAs productions in different cell types was compared. For the first time 5′ copy-back DI-RNAs specific binding to RIG-I, MDA5 and LGP2 was assessed and linked to functional outcome in type-I IFN signalling. The inventors provide a composition of products comprising at least (i) a mixture of particles of a rescued recombinant MV-derived virus encoding at least one antigen (ii) a recombinant and/or purified protein, comprising at least one antigen. Regardless of the presentation of the products, and in particular regardless of whether the products are separated or readily separable or presented as a mixture.