Dengue Virus-Like Particles for Safer Multiserotype Immunity
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Solution Overview
Problem
Current dengue fever vaccines face challenges due to the risk of vaccine-related adverse events and the need to induce a long-lasting protective immune response against all four dengue serotypes, while existing vector control measures are inadequate for prevention.
Innovation Solution
Development of virus-like particles (VLPs) comprising dengue virus structural proteins, specifically prM and envelope regions, which spontaneously assemble into non-infectious particles, allowing for the production of vaccines and antibodies to enhance immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If attenuated live vaccines are used to induce protective immune response, then immunogenicity is improved, but risk of vaccine-related adverse events increases
Solution Approach 1:
The patent creates virus-like particles that copy the structural features of authentic dengue viruses (including envelope proteins and prM proteins) to induce immune response, but without containing any viral genome, thus eliminating infectivity while maintaining immunogenicity
Solution Approach 2:
The invention extracts only the essential structural components (envelope proteins and prM proteins) from the viral particle, removing the harmful viral genome while retaining the protective antigens needed to induce neutralizing antibodies
2Ease of manufacture
If VLPs are produced without amino acid modifications, then production simplicity is improved, but intracellular retention of envelope protein occurs reducing secretion
Solution Approach 1:
The patent introduces specific amino acid modifications in the transmembrane domain of the envelope protein (such as adding positively charged residues like lysine or arginine) to alter the charge characteristics and facilitate interaction with negatively charged phospholipids in the endosomal membrane, thereby enhancing secretion efficiency
Solution Approach 2:
The invention applies targeted amino acid modifications only in specific regions of the envelope protein (transmembrane domain) rather than throughout the entire protein sequence, maintaining production simplicity while locally improving secretion properties
Data Source
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AI summary
The present application provides a virus like particle comprising one or more flavivirus structural proteins, and a composition or vaccine comprising thereof, its use in the prevention or treatment of flavivirus infection. The flavivirus structural protein contains at least one amino acid alteration in the envelope region. Examples of flavivirus contains dengue virus.