TLR7/8-Activating Substituted Pyrimidines for Subunit Vaccine Adjuvants
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Solution Overview
Problem
Subunit vaccines comprising partial peptides have lower immuno-stimulating ability compared to live or inactivated vaccines, necessitating the development of a new vaccine adjuvant that activates Toll-like Receptors 7 and/or 8 to enhance immunogenicity.
Innovation Solution
A conjugated compound, where a pyrimidine compound is chemically linked to an oily substance via a spacer, enhancing the adjuvant activity beyond that of either component alone.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If subunit vaccines comprising partial peptides are used, then safety and production process are improved, but immuno-stimulating ability deteriorates
Solution Approach 1:
The patent applies composite materials by combining a pyrimidine compound (TLR7/8 agonist) with an oily substance (squalene) to form a conjugated compound. This composite structure integrates the immuno-stimulating capability of the pyrimidine compound with the adjuvant properties of squalene, thereby enhancing the overall immunogenicity of subunit vaccines while maintaining their safety and production advantages.
2Object-generated harmful factors
If TLR7/8 agonists are used alone, then immune activation is improved, but adjuvant activity is insufficient
Solution Approach 1:
The patent merges the TLR7/8 agonist (pyrimidine compound) with squalene through chemical conjugation. This combination integrates the immune activation function of the pyrimidine compound with the adjuvant properties of squalene, creating a compound with enhanced and synergistic adjuvant activity that overcomes the limitations of using either component alone.
3Ease of manufacture
If conventional adjuvants like Alum are used, then production cost is reduced, but immune response enhancement is insufficient
Solution Approach 1:
The patent changes the chemical and functional parameters of the adjuvant system by developing a conjugated compound with specific molecular structure (pyrimidine-squalene conjugate). This parameter change enables the adjuvant to activate TLR7/8 pathways and produce type I interferon, representing a significant improvement in immune response enhancement compared to conventional adjuvants like Alum.
Data Source
AI summary
The present invention provides a compound of the formula (1):wherein X, R1, R2, R3, R4, R5, R6, Y1, Y2, L, and m are as defined in the description, and a pharmaceutically acceptable salt thereof, which are useful as a vaccine adjuvant.