Chimeric HA Vaccination Regimens for Broad Influenza Immunity

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Solution Overview

Problem

Current influenza vaccination strategies struggle to induce broad immunity against various strains and subtypes of influenza virus due to antigenic drift and the inability to predict pandemic strains, leading to inefficiencies in vaccine efficacy and the need for cross-protective vaccines.

Innovation Solution

Immunization regimens involving chimeric or headless hemagglutinin (HA) constructs and neuraminidase (NA) immunogens, administered in various forms, to elicit potent and broadly neutralizing antibodies against the stem domain of HA and NA, potentially combined with live and inactivated influenza viruses, to enhance immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If current influenza vaccination strategies use traditional vaccine formulations, then vaccine production is straightforward, but the ability to induce broad immunity against various strains and subtypes is limited

Engineering Contradiction:

Improvecross-protection against diverse influenza strainsVSAvoidvaccine formulation complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The hemagglutinin protein is segmented into head and stem domains. The vaccine focuses on the conserved stem domain (amino acids 110-317) while removing or modifying the variable head domain, thereby segmenting the antigen to highlight the conserved protective epitopes that provide broad cross-protection against diverse influenza strains

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The vaccine uses chimeric hemagglutinin constructs that combine conserved stem domain sequences from different influenza subtypes (e.g., H1, H3, H5, H7) into a single immunogen. This composite approach allows the vaccine to elicit antibodies that recognize multiple influenza subtypes simultaneously, enhancing cross-protection without requiring separate vaccines for each strain

Inventive Principle:

Principle #40Composite materials

2Reliability

If vaccine strains are selected based on surveillance predictions, then vaccine manufacturing can be planned in advance, but accuracy in predicting pandemic strains is insufficient

Engineering Contradiction:

Improvevaccine efficacyVSAvoidtime for strain selection and manufacturing

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The vaccine is designed in advance to target conserved stem domain epitopes that are present across multiple influenza subtypes and pandemic candidates (H5N1, H7N9, etc.). This preliminary design approach eliminates the need for annual strain selection and allows manufacturing planning well before any potential pandemic strain emerges, providing reliable cross-protection regardless of which strain causes the next pandemic

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The chimeric hemagglutinin stem domain vaccine serves multiple functions simultaneously: it protects against seasonal influenza strains and provides cross-protection against pandemic candidate strains (H5N1, H7N9, H9N2). This universal approach replaces the need for separate strain-specific vaccines, improving reliability while eliminating the time loss associated with predicting and selecting specific pandemic strains

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Adaptability or versatility

If traditional whole virus vaccines are used, then manufacturing is simpler, but the immune response is dominated by head domain antibodies which do not provide cross-protection

Engineering Contradiction:

Improvebroad neutralizing antibody responseVSAvoidmanufacturing complexity

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The variable head domain (amino acids 1-109) is removed or significantly modified from the hemagglutinin structure. This extraction eliminates the dominant but non-protective head domain epitopes that cause immunodominance, allowing the immune system to focus on the conserved stem domain epitopes that provide broad cross-protection against diverse influenza strains

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The vaccine enhances the immunogenicity of the stem domain region specifically by removing the head domain and potentially adding adjuvants or modifying the stem domain structure. This local enhancement ensures that antibodies are directed against the conserved stem domain (amino acids 110-317) rather than the variable head domain, achieving broad neutralizing antibody responses without requiring complex manufacturing processes

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20260048114A1Influenza virus vaccination regimens

Publication Date: 2026.02.19 MT SINAI SCHOOL OF MEDICINE

AI summary

Provided herein are immunization regimens for inducing an immune response (e.g., an antibody response) against influenza virus. In specific aspects, the immunization regimens involve the administration of a chimeric hemagglutinin (HA), a headless HA or another influenza virus stem domain based construct (e.g., the HA stem domain or a fragment thereof) to a subject. In certain aspects, the immunization regimens also involve the administration of an influenza virus neuraminidase immunogen.