Optimized HA Polypeptides for Broadly Reactive Influenza Immunity

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Solution Overview

Problem

Current influenza vaccines are limited in their ability to induce broad protective immunity, particularly for H5N1 and H1N1 influenza viruses, with inactivated vaccines eliciting poor cellular immune responses and live virus vaccines being unsuitable for immunocompromised or pregnant individuals.

Innovation Solution

Development of computationally optimized H5N1 and H1N1 influenza HA polypeptides, which are used to generate recombinant proteins and virus-like particles (VLPs) to elicit a broadly reactive immune response, including the use of optimized amino acid sequences and vectors for expression in mammalian cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If inactivated influenza vaccines are used, then humoral immune responses are efficiently induced, but cellular immune responses are generally poor

Engineering Contradiction:

Improveantibody productionVSAvoidcellular immune response

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent combines HA polypeptides from multiple influenza virus strains (H5N1, H1N1, and other subtypes) into a single composite vaccine antigen. This composite approach simultaneously presents diverse epitopes to the immune system, enabling both humoral (antibody) and cellular immune responses against multiple influenza strains, thereby resolving the contradiction between antibody production and cellular immune response quality

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If live virus vaccines are used, then broad immune coverage is achieved, but they cannot be administered to immunocompromised or pregnant patients

Engineering Contradiction:

Improveimmune coverageVSAvoidinfection risk for vulnerable populations

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts only the essential immunogenic components (HA polypeptides) from the complete influenza virus, creating a recombinant protein vaccine. This extraction removes the harmful replication capability of live viruses while retaining the ability to induce broad immune coverage, making the vaccine safe for immunocompromised and pregnant patients while maintaining adaptability against multiple strains

Inventive Principle:

Principle #2Taking out (Extraction)

3Loss of information

If conventional HA protein alignment methods are used, then sequence comparison is performed, but broadly reactive antigen optimization is insufficient

Engineering Contradiction:

Improvesequence diversityVSAvoidimmune response breadth

Core Design Contradiction:

Loss of informationVSProductivity

Solution Approach 1:

The patent applies computational optimization to systematically analyze and modify HA protein sequences from multiple influenza strains. By changing key amino acid parameters at conserved epitopic regions and using algorithms to identify optimal sequences, the method transforms conventional sequence comparison into a predictive design process that generates HA polypeptides with enhanced broadly reactive immune responses across H5N1, H1N1, and other influenza subtypes

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS9555095B2Computationally optimized broadly reactive antigens for H5N1 and H1N1 influenza viruses

Publication Date: 2017.01.31 UNIV OF PITTSBURGH OF THE COMMONWEALTH SYST OF HIGHER EDUCATION

AI summary

Described herein is the generation of optimized H5N1 and H1N1 influenza HA polypeptides for eliciting a broadly reactive immune response to influenza virus isolates. The optimized HA polypeptides were developed through a series of HA protein alignments, and subsequent generation of consensus sequences, based on H5N1 and H1N1 influenza isolates. Provided herein are optimized H5N1 and H1N1 influenza HA polypeptides, and compositions, fusion proteins and VLPs comprising the HA polypeptides. Further provided are codon-optimized nucleic acid sequences encoding the HA polypeptides. Methods of eliciting an immune response against influenza virus in a subject are also provided by the present disclosure.