Ferritin HA Stem Nanoparticles for Broad Group 2 Influenza Protection

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Solution Overview

Problem

Current influenza vaccines are strain-specific and face challenges in manufacturing, with limited capacity and efficacy against heterologous strains, particularly Group 2 influenza viruses, and there is a need for a vaccine that can induce broadly neutralizing antibodies against these viruses.

Innovation Solution

Development of recombinant proteins comprising a Group 2 influenza hemagglutinin (HA) protein with the head region replaced by a linker and fused to a monomeric subunit like ferritin, forming nanoparticles that display the conserved stem region, eliciting a robust immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current influenza vaccines are updated annually to reflect predicted HA and neuraminidase, then vaccine efficacy against circulating viruses is improved, but the complexity of vaccine development and manufacturing increases

Engineering Contradiction:

Improvevaccine efficacyVSAvoidvaccine development complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and focuses solely on the conserved HA stem region, removing the variable head region that causes antigenic drift. This extraction allows the vaccine to target a constant epitope that remains effective across different influenza strains and years, eliminating the need for annual updates while maintaining efficacy.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The HA stem region serves as a universal target that can neutralize multiple influenza virus subtypes and strains simultaneously. By designing a vaccine around this conserved region, a single vaccine formulation can provide protection against both seasonal and pandemic influenza viruses, including Group 2 influenza viruses, without requiring strain-specific formulations.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If the immunodominant head region of HA is removed and stem domain is stabilized, then broadly neutralizing antibody elicitation is improved, but the immunogenicity of the HA stem decreases

Engineering Contradiction:

Improvebroad neutralizing capabilityVSAvoidimmune response robustness

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent creates a composite structure by fusing the stabilized HA stem domain with ferritin, a highly immunogenic protein shell. This composite nanoparticle combines the broad neutralizing capability of the HA stem with the strong immune stimulating properties of ferritin, achieving both versatility and robust immune response simultaneously.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The ferritin nanoparticle acts as an intermediary carrier that presents the HA stem epitope in a highly immunogenic context. The ferritin structure serves as a mediator that enhances the immunogenicity of the otherwise weak HA stem antigen, enabling robust antibody elicitation while maintaining broad neutralizing activity.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If influenza vaccine is updated each year to reflect predicted HA, then protection against circulating viruses is maintained, but manufacturing capacity and production time are limited

Engineering Contradiction:

Improvevaccine protectionVSAvoidmanufacturing capacity

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent segments the HA protein into two functional regions: the variable head region (discarded) and the conserved stem region (retained). This segmentation allows the vaccine to focus exclusively on the stable stem region that provides consistent protection across strains, enabling standardized manufacturing that does not require annual reformulation while maintaining high productivity.

Inventive Principle:

Principle #1Segmentation

4Adaptability or versatility

If recombinant HA stem nanoparticles are used, then broad protection against Group 2 influenza viruses is achieved, but the complexity of protein engineering and nanoparticle formation increases

Engineering Contradiction:

Improvebroad virus protectionVSAvoidprotein engineering complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary stabilization of the HA stem domain through specific amino acid mutations before fusion with ferritin. This preliminary action ensures that the stem region adopts the correct pre-fusion conformation and is ready for nanoparticle assembly, simplifying the overall engineering process by preparing the protein in advance rather than optimizing it during the complex nanoparticle formation step.

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS12527857B2Stabilized group 2 influenza hemagglutinin stem region trimers and uses thereof

Publication Date: 2026.01.20 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

Vaccines that elicit broadly protective anti-influenza antibodies. The vaccines comprise nanoparticles that display HA trimers from Group 2 influenza virus on their surface. The nanoparticles are fusion proteins comprising a monomeric subunit (e.g., ferritin) joined to stabilized stem regions of Group 2 influenza virus HA proteins. The fusion proteins self-assemble to form the HA-displaying nanoparticles. Also provided are fusion proteins, and nucleic acid molecules encoding such proteins, and assays using nanoparticles of the invention to detect anti-influenza antibodies.