Lentiviral Vector Expressing JEV prM and E Proteins
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Solution Overview
Problem
Current vaccines for Japanese encephalitis (JE) lack long-term immunity and pose risks due to the potential reversion of live-attenuated vaccine strains to virulence, and they are costly, necessitating a more effective and safer immunogenic composition for preventing JE infection across multiple genotypes.
Innovation Solution
A recombinant lentiviral vector expressing the precursor of membrane (prM) and envelope (E) proteins of the Japanese encephalitis virus (JEV), or immunogenic fragments thereof, is developed, which primes and boosts antigen-specific humoral responses, providing broad neutralizing immunity against multiple JEV genotypes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If live-attenuated vaccine strains are used, then immunogenicity is improved, but safety deteriorates due to potential reversion to virulence
Solution Approach 1:
The patent extracts only the essential immunogenic components (prM and E proteins) from the complete JEV structure, expressing them as recombinant proteins in a lentiviral vector system. This extraction eliminates the replicative capacity and virulence factors while retaining the protective antigens, thereby maintaining immunogenicity without the risk of reversion to virulence.
Solution Approach 2:
The patent uses a lentiviral vector as an intermediary carrier to deliver JEV prM and E protein genes into host cells. This intermediary system enables controlled expression of immunogenic proteins without introducing live attenuated virus, thus achieving immunization while avoiding the safety risks associated with live-attenuated vaccine strains.
2Quantity of substance
If conventional vaccines are used, then cost is reduced, but immunity duration deteriorates (lack of long-term immunity)
Solution Approach 1:
The patent employs a lentiviral vector system that enables dynamic and sustained expression of JEV antigens through integration into host cell genome or persistent episomal maintenance. This dynamic expression system provides prolonged antigen exposure to the immune system, resulting in long-term immunity that overcomes the limitation of conventional vaccines.
3Adaptability or versatility
If conventional vaccines are used, then coverage is limited, but adaptability deteriorates (cannot protect against multiple genotypes)
Solution Approach 1:
The patent designs a universal lentiviral vector platform that can accommodate JEV prM and E protein genes from different genotypes (G1, G3, G5). This multi-functional vector system enables the development of vaccines protective against multiple JEV genotypes by simply changing the inserted antigen genes, thereby achieving broad adaptability without proportionally increasing overall system complexity.
Data Source
AI summary
The present invention relates to a lentiviral vector-based Japanese encephalitis (JE) immunogenic composition. The present invention is directed to a recombinant lentiviral vector expressing the precursor of membrane (prM) and the envelope (E) protein, in particular glycoprotein of a Japanese encephalitis virus (JEV) or immunogenic fragments thereof. The present invention also provides cells expressing the lentiviral vector, uses and methods to prevent a JEV infection in a mammalian host, especially in a human or an animal host, in particular a pig or a piglet, preferably a domestic pig or a domestic piglet.