Multivalent HPV VLP Composition for High-Yield L1 Expression
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Solution Overview
Problem
Existing HPV vaccine production systems face challenges in achieving high yields of virus-like particles, particularly in prokaryotic expression systems, which results in complicated purification processes and limited coverage for HPV types not included in current commercial vaccines.
Innovation Solution
A multivalent HPV immunogenic composition comprising HPV virus-like particles assembled from L1 proteins of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, and optionally other pathogenic HPV types, using chimeric L1 proteins with optimized N- and C-terminal fragments for improved expression and solubility, assembled into correctly formed disulfide-bonded icosahedrons.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If prokaryotic expression systems are used for HPV L1 protein production, then production cost is reduced, but manufacturing precision deteriorates due to complicated purification processes and limited VLP yield
Solution Approach 1:
The L1 protein is divided into two functional segments: an N-terminal fragment (amino acids 1-280) responsible for VLP assembly and immunogenicity, and a C-terminal fragment (amino acids 281-499) containing the nuclear localization signal. This segmentation allows the N-terminal fragment to self-assemble into VLPs in prokaryotic systems without requiring the full-length protein, thereby simplifying purification while maintaining immunogenicity and increasing yield.
Solution Approach 2:
The nuclear localization signal (NLS) at the C-terminus of the L1 protein is extracted and removed. Since the NLS is not required for VLP formation or immunogenicity, its removal simplifies the protein structure, facilitates purification in prokaryotic systems, and eliminates potential interference with VLP self-assembly, while the N-terminal fragment retains all necessary functions for vaccine efficacy.
2Reliability
If current commercial HPV vaccines are used, then immunogenicity is ensured, but adaptability deteriorates due to limited coverage for HPV types not included in current vaccines
Solution Approach 1:
The vaccine composition is designed to be multivalent, incorporating VLPs from multiple HPV types (6, 11, 16, 18, 31, 33, 45, 52, and 58) in a single formulation. This universal approach provides broad-spectrum protection against both low-risk and high-risk HPV types, extending coverage beyond what any single commercial vaccine offers, while each VLP component maintains its specific immunogenicity for the corresponding HPV type.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition achieves high yields of HPV virus-like particles, enabling broad-spectrum prevention of HPV-related diseases by self-assembling into functional virus-like particles with enhanced expression and solubility, suitable for vaccine production.
Implementation Method 1
assembled from L1 proteins of HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58... assembled into correctly formed disulfide-bonded icosahedrons
Data Source
AI summary
The present invention relates to a multivalent HPV immunogenic composition for preventing human papillomavirus (HPV) related diseases or infections and uses thereof. Said multivalent HPV immunogenic composition comprises: HPV virus-like particles assembled from L1 proteins of HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and one or more HPV virus-like particles assembled from L1 proteins of other pathogenic HPV types. In one embodiment, said one or more other pathogenic HPV types are selected from HPV Types 35, 39, 51, 56 and 59. In one embodiment, at least one of said HPV virus-like particles is a chimeric HPV virus-like particle, and said chimeric HPV virus-like particle comprises one or more chimeric HPV L1 proteins.