Attenuated Virus Codon Pair Bias Dengue Vaccine
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Solution Overview
Problem
Current vaccines are unable to effectively protect against all serotypes of dengue virus, and existing technologies fail to provide a marketable vaccine capable of preventing human infection by dengue virus serotypes, leading to significant morbidity and mortality worldwide.
Innovation Solution
Development of attenuated viruses with modified viral genomes that have altered codon pair bias, allowing the viruses to be attenuated in one host while maintaining efficiency in another, specifically designed to elicit a protective immune response across multiple dengue virus serotypes by modifying codon pair bias in virus protein-encoding sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the virus uses codon pairs optimized for efficient replication in insect hosts, then replication efficiency in insect hosts is improved, but the virus becomes attenuated in mammalian hosts
Solution Approach 1:
The patent applies parameter changes by modifying the codon pair composition in the viral genome. Specifically, synonymous codons are rearranged to alter codon pair bias, changing the nucleotide sequence parameters while maintaining the same amino acid sequence. This allows the virus to be optimized for replication in insect hosts (improving productivity) while simultaneously being attenuated in mammalian hosts (reducing pathogenicity), thereby resolving the technical contradiction between replication efficiency and viral harmlessness.
2Object-affected harmful factors
If the virus is attenuated in mammalian hosts to ensure safety for vaccine use, then safety is improved, but replication efficiency in mammalian hosts deteriorates
Solution Approach 1:
The patent resolves this contradiction by changing the codon pair parameters in the viral genome. By rearranging synonymous codons to create specific codon pair biases, the virus achieves attenuation in mammalian hosts (improving safety) while maintaining adequate replication efficiency through the same genetic modifications. The codon pair rearrangement creates a balance where the virus is safe for human use but retains sufficient replicative capability for vaccine efficacy.
3Reliability
If existing vaccines are designed to provide protection against multiple dengue virus serotypes, then vaccine effectiveness is improved, but the complexity of the vaccine system increases
Solution Approach 1:
The patent applies universality by creating a single attenuated virus strain that can serve multiple functions: it provides protection against multiple dengue virus serotypes (1-4) while maintaining safety through attenuation in mammalian hosts. This multi-functional approach eliminates the need for separate vaccines for different serotypes, thereby improving vaccine effectiveness without proportionally increasing system complexity.
Data Source
AI summary
This invention provides an attenuated virus comprising a modified viral genome engineered to containing multiple nucleotide substitutions that reduce the codon pair bias of a virus protein encoding sequence relative to a first host while the codon pair bias relative to a second host is not substantially reduced. In another embodiment, the invention provides an attenuated virus comprising modified viral genome engineered to containing multiple nucleotide substitutions that reduce the codon pair bias of a virus protein-encoding sequence relative to a first host and a second host. The attenuated virus may be used in a vaccine composition for inducing a protective immune response in a subject. The invention also provides a method of synthesizing the attenuated virus. Further, this invention further provides a method for preventing a subject from becoming afflicted with a virus-associated disease comprising administering to the subject a prophylactically effective dose of a vaccine composition comprising the attenuated virus.