Attenuated Influenza A Virus Vector for Broad Cross-Protective Immunity
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Solution Overview
Problem
Current influenza vaccines are ineffective in providing long-lasting, broad cross-protective immunity against evolving influenza viruses, particularly due to high variability of surface antigens, leading to frequent updates and limited protection against new pandemic strains, and existing viral vectors face challenges such as pre-existing immunity, safety concerns, and low packing capacity.
Innovation Solution
Development of an attenuated influenza A virus with a chimeric NS fragment, including a truncated NS1 protein and a heterologous Nep gene sequence, which induces a cross-protective response against both influenza A and B viruses, characterized by temperature-sensitivity and reduced replication in animal organisms, enabling safe use as a universal vaccine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional killed or live vaccines are used, then they can provide some immune protection, but they cannot induce broad cross-protective immunity against evolving influenza strains due to antigenic drift
Solution Approach 1:
The invention extracts the variable surface antigens (HA and NP proteins) that cause antigenic drift and replaces them with conserved internal viral proteins (PB1, PB2, PA, M1, M2, NS1). This extraction of the problematic variable components and replacement with stable conserved components enables broad cross-protection against different influenza strains while maintaining reliable immune response.
Solution Approach 2:
The vaccine composition uses conserved internal proteins (PB1, PB2, PA, M1, M2, NS1) that are common across multiple influenza A and B virus subtypes. This universal approach allows a single vaccine formulation to provide cross-protective immunity against diverse influenza strains, including potential pandemic strains, without needing frequent updates.
2Reliability
If live attenuated viruses are used as vectors, then they can induce strong and long-lasting immune responses, but they face safety concerns regarding replication in animal organisms
Solution Approach 1:
The invention uses a replication-defective influenza virus vector that cannot replicate independently in animal organisms. The vector's inability to replicate (which would be a harmful factor) is converted into a safety benefit, while still maintaining the ability to deliver viral antigens and induce strong immune responses. The vector requires co-infection with a helper virus to replicate, providing built-in safety control.
Solution Approach 2:
The replication-defective influenza virus vector acts as an intermediary delivery system that transports conserved viral antigens to the immune system without causing uncontrolled replication. The vector mediates antigen delivery while its replication defect prevents harmful over-replication, and it requires a helper virus as an intermediary to complete the replication cycle under controlled conditions.
3Adaptability or versatility
If other viral vectors (poxviruses, adenoviruses, Newcastle disease virus) are used, then they can deliver foreign genetic material, but they face limitations such as pre-existing immunity, low packing capacity, or insufficient safety data
Solution Approach 1:
The influenza virus vector is engineered to express multiple conserved antigens (PB1, PB2, PA, M1, M2, NS1) simultaneously, providing multi-functional protection against both influenza A and B viruses. This universal approach consolidates multiple protective functions into a single vector system, avoiding the need for multiple separate vaccines or complex vector combinations.
Solution Approach 2:
The invention modifies the influenza virus vector parameters by deleting the HA and NP genes (which cause antigenic drift) and replacing them with conserved internal protein genes. This parameter change transforms the vector into a platform that can deliver multiple conserved antigens while avoiding the pre-existing immunity and packing capacity limitations of other viral vectors.
Data Source
AI summary
The present invention relates to the field of medicine and virology. An attenuated influenza A virus, an influenza virus vector based thereon, and a pharmaceutical composition comprising thereof are provided, which can be used for the prevention and/or treatment of an infectious disease. In addition, the present invention relates to an attenuated influenza A virus, an influenza virus vector based thereon, and a pharmaceutical composition comprising thereof, which can be used for the treatment of oncological diseases.