Group 2 Influenza HA Stem Vaccines for Broad Strain Protection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current influenza vaccines provide limited protection against diverse influenza strains due to antigenic drift and immunodominance of the HA head domain, necessitating annual updates and offering minimal cross-protection, especially against group 2 viruses like H3N2 and H7 strains.
Innovation Solution
Development of monomeric and multimeric HA stem polypeptides lacking the globular head region, stabilized with specific modifications to present conserved epitopes of the HA stem domain, which can be recombinantly expressed and induce a robust, broadly neutralizing antibody response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional influenza vaccines targeting the HA head domain are used, then they provide protection against specific circulating strains, but they offer limited cross-protection against diverse influenza strains due to antigenic drift and immunodominance
Solution Approach 1:
The patent extracts the conserved HA stem domain from the variable HA head domain to create a vaccine antigen that specifically targets the stable, conserved region. This extraction eliminates the problem of antigenic drift in the head domain while maintaining immunogenicity through the stem domain's conserved epitopes, thereby achieving broad cross-protection across diverse influenza strains.
Solution Approach 2:
The patent applies local quality by focusing the immune response on a specific local region (the HA stem domain) that possesses desirable properties (conservation across strains) rather than using the entire HA protein. The stem domain's stable sequence and structure provide consistent epitopes that elicit broadly neutralizing antibodies, resolving the contradiction between strain-specific protection and cross-protection.
2Reliability
If seasonal influenza vaccines are updated annually to match circulating strains, then they maintain effectiveness against current strains, but they require continuous monitoring and production updates which consume time and resources
Solution Approach 1:
The patent employs preliminary action by pre-identifying and utilizing the conserved HA stem domain epitopes that are invariant across influenza strains. This preliminary characterization of conserved regions allows the development of a universal vaccine platform that does not require annual updates, as the stem domain's conservation provides inherent stability against antigenic drift and eliminates the need for continuous strain monitoring and vaccine reformulation.
3Strength
If the HA head domain is included in the vaccine antigen, then it provides strong immunogenicity, but it induces strain-specific antibody responses that do not cross-react with other influenza strains
Solution Approach 1:
The patent extracts only the HA stem domain from the complete HA protein, deliberately excluding the immunodominant but variable head domain. This extraction maintains immunogenicity through the stem domain's conserved epitopes while eliminating the source of strain-specific responses, thereby achieving both strong immunogenicity and broad cross-reactivity in a single targeted antigen.
Solution Approach 2:
The patent applies local quality by directing the immune response to a specific local region (the HA stem domain) that possesses the desirable property of sequence conservation across strains. This localized targeting ensures that antibodies generated against the stem domain are broadly neutralizing and cross-reactive, resolving the contradiction between strong immunogenicity and antibody cross-reactivity.
Data Source
AI summary
Provided herein are group 2 influenza hemagglutinin stem polypeptides, nucleic acids encoding said polypeptides, vectors comprising said nucleic acid and pharmaceutical compositions comprising the same, as well as methods of their use, in particular in the prevention and/or treatment of influenza virus infections.