Live Attenuated RSV Vaccine Codon Deoptimization
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Solution Overview
Problem
Current live attenuated RSV vaccines face challenges with suboptimal immunogenicity and stability issues in infants, leading to genetic reversion and inadequate protection against RSV infections.
Innovation Solution
A live attenuated RSV vaccine is administered intranasally with specific doses and schedules to children between 6 and 59 months of age, utilizing codon-deoptimized NS1 and NS2 genes and a mutated F gene to enhance immunogenicity and stability, comprising genome sequences such as SEQ ID NOs: 6, 9, and 20, and administered via drops or nasal atomizer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If live attenuated RSV vaccine is administered to infants, then immunogenicity is improved, but stability deteriorates leading to genetic reversion
Solution Approach 1:
The patent segments the RSV genome by deleting specific genes (NS1, NS2, and F) to create an attenuated vaccine strain. This segmentation approach reduces viral stability while improving immunogenicity, as the deleted genes prevent genetic reversion to wild-type sequences while maintaining the ability to elicit protective immune responses in infants.
2Object-affected harmful factors
If attenuated RSV vaccine is used, then safety is improved, but immunogenicity deteriorates
Solution Approach 1:
The patent applies local quality by selectively deleting specific genes (NS1, NS2, F) from the RSV genome to create an attenuated strain that is safe for infants while maintaining immunogenicity. The deleted genes are specifically chosen to reduce viral fitness and prevent reversion, while preserving the ability to elicit protective immune responses through the remaining viral components.
3Ease of operation
If conventional RSV vaccine dosing is used, then ease of administration is maintained, but effectiveness deteriorates in pediatric population
Solution Approach 1:
The patent changes the dosing parameters by establishing age-specific dosing regimens for infants and children. The vaccine is administered at different doses based on age groups (e.g., 10^3-10^6 PFU for infants 6-24 months, with adjustments for older children). This parameter optimization ensures effectiveness in the pediatric population while maintaining ease of administration through simplified dosing schedules.
Data Source
AI summary
The invention relates generally to pediatric dosing regimens for RSV vaccines.