HPV58 L1-L2 Chimeric Protein for Broad-Spectrum Vaccine
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Solution Overview
Problem
Current HPV vaccines, particularly those based on L1 virus-like particles, have limited protection range and cannot effectively prevent infections from all high-risk HPV types, and vaccines using L2 proteins with RG-1 epitope peptides show poor immunogenicity and limited cross-neutralization activity.
Innovation Solution
Development of a human papillomavirus chimeric protein comprising HPV type 58 L1 protein with an inserted polypeptide from HPV type 16 L2 protein, specifically designed to enhance immunogenicity and induce broad-spectrum neutralizing antibodies across multiple HPV types by optimizing the insertion site and sequence within the L1 protein framework.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If L1 virus-like particles are used as vaccine basis, then high immunogenicity is achieved, but protection range is limited to specific HPV types
Solution Approach 1:
The patent combines L1 and L2 proteins into a chimeric protein structure where L1 provides immunogenicity and L2 provides broad-spectrum recognition. The chimeric protein contains an N-terminal L1 domain and a C-terminal L2 domain with RG-1 epitope, enabling simultaneous induction of type-specific and cross-neutralizing antibodies against multiple HPV types
Solution Approach 2:
The chimeric protein vaccine achieves multi-functionality by incorporating conserved RG-1 epitope sequences from L2 that recognize common structures across different HPV types. This allows a single vaccine formulation to provide protection against multiple high-risk HPV types including 16, 18, 31, 33, 45, 52, and 58
2Adaptability or versatility
If L2 protein with RG-1 epitope is used, then broad-spectrum recognition is achieved, but immunogenicity is poor
Solution Approach 1:
The chimeric protein merges the high immunogenicity L1 protein with the broad-spectrum L2 RG-1 epitope. The L1 domain serves as a strong immunogen to drive antibody production, while the L2 domain provides cross-neutralizing capability, resolving the contradiction between immunogenicity and cross-protection
3Adaptability or versatility
If multiple L1VLP types are combined to expand protection, then coverage increases, but vaccine complexity increases
Solution Approach 1:
Instead of combining multiple L1VLP types, the patent creates a universal chimeric protein that recognizes multiple HPV types through the conserved L2 RG-1 epitope. This single vaccine formulation provides broad-spectrum protection without the complexity of multi-component formulations
Data Source
AI summary
Provided are an HPV chimeric protein and a use thereof. The HPV chimeric protein of the present invention comprises an HPV58 L1 protein or a mutant thereof and a polypeptide derived from a HPV16 L2 protein and inserted into a surface region of the HPV58 L1 protein or the mutant thereof, or consists of the polypeptide, wherein an amino acid sequence of the HPV58 L1 protein is as shown in SEQ ID No. 1 and an amino acid sequence of the HPV16 L2 protein is as shown in SEQ ID No. 2.