Recombinant Influenza Virus M2SR Platform for Bivalent Vaccines
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Solution Overview
Problem
Current vaccines for coronavirus and influenza often fail to induce robust mucosal and cell-mediated immune responses, which are crucial for providing long-lasting protection against these pathogens.
Innovation Solution
Development of a bivalent coronavirus/influenza virus vaccine using a Single-Replication (SR) platform, specifically the M2SR platform, which expresses a secreted version of the spike protein of coronavirus and includes influenza virus proteins like HA and NA, to mimic natural infection and stimulate multiple immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional coronavirus and influenza vaccines are used, then vaccination can be administered, but robust mucosal and cell-mediated immune responses are not induced
Solution Approach 1:
The vaccine platform segments the immune response into multiple components by expressing multiple viral antigens (spike protein, HA, NA) simultaneously from a single viral vector, enabling comprehensive immune stimulation without requiring multiple separate vaccine formulations
Solution Approach 2:
The recombinant influenza virus serves as a composite platform combining coronavirus spike protein sequences with influenza virus genetic elements (M2 protein, HA, NA segments), creating a single-virus multivalent vaccine that elicits broad immune responses
2Reliability
If the M2SR platform expresses multiple viral proteins to mimic natural infection, then multiple immune responses are stimulated, but the risk of viral replication and recombination increases
Solution Approach 1:
The M2 ion channel domain is removed or inactivated from the M2 protein sequence, extracting the essential ion channel function that enables viral replication while retaining the ability to express and present viral antigens for immune stimulation
Solution Approach 2:
A single-replication (SR) platform acts as an intermediary mechanism, allowing one round of viral replication to express antigens and stimulate immune responses, but preventing subsequent replication cycles that could lead to viral evolution or recombination
3Ease of operation
If a single-dose vaccine is designed for convenience, then administration complexity is reduced, but achieving long-lasting immunity with robust mucosal and cell-mediated responses becomes more difficult
Solution Approach 1:
Multiple immune-stimulating components (spike protein, HA, NA antigens) are merged into a single recombinant viral vector that can be administered in one dose, combining the benefits of multivalent vaccination with single-dose convenience
Solution Approach 2:
The recombinant influenza virus platform serves multiple functions simultaneously: it acts as a delivery vehicle for coronavirus antigens, provides influenza antigen exposure, mimics natural viral infection to stimulate comprehensive immune responses, and enables single-dose administration
Data Source
AI summary
The invention provides a composition useful to prepare influenza vaccine viruses, e.g., in the absence of helper virus, which includes internal viral segments from an influenza virus vaccine strain or isolate, e.g., one that is safe in humans, for instance, one that does not result in significant disease, and encodes a heterologous antigen.