Chimeric HPV58 L1 Protein for Broad Cross-Protection
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Solution Overview
Problem
Current HPV vaccines have limited protection range, as they primarily induce neutralizing antibodies against a single HPV type, offering low cross-protection against other HPV types, necessitating the inclusion of multiple HPV types in vaccines to broaden protection, which increases production costs and potential safety concerns.
Innovation Solution
A mutated HPV58 L1 protein with specific mutations, such as N-terminal truncation and amino acid substitutions from HPV33 and HPV52, induces high-titer neutralizing antibodies against multiple HPV types, providing protection comparable to a mixture of VLPs from individual HPV types at a single immunizing dose.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If VLPs of multiple HPV types are combined in vaccines to broaden protection range, then the protection range is improved, but the production cost increases and safety problems may occur
Solution Approach 1:
The patent creates a chimeric VLP that performs multiple protective functions simultaneously. By fusing L1 proteins from different HPV types (e.g., HPV16, HPV18, HPV31, HPV45, HPV52, HPV58), the single VLP structure presents multiple viral epitopes that can induce neutralizing antibodies against multiple HPV types, eliminating the need for separate VLP components for each type.
Solution Approach 2:
The patent merges the L1 protein sequences of multiple HPV types into a single chimeric L1 protein. This fusion approach combines the protective antigens of different HPV types into one integrated structure, which then self-assembles into a single type of VLP that provides cross-protection against all included HPV types.
2Adaptability or versatility
If VLPs of multiple HPV types are combined in vaccines to broaden protection range, then the protection range is improved, but safety problems may occur due to increased immunizing dose
Solution Approach 1:
The chimeric VLP serves as a universal vaccine component that protects against multiple HPV types simultaneously. The fused L1 protein structure maintains the ability to self-assemble into proper VLP morphology while presenting epitopes from multiple HPV types, reducing the need for high doses of multiple different VLPs.
Solution Approach 2:
The patent modifies the molecular structure of the L1 protein by changing its amino acid sequence composition. By incorporating specific regions from different HPV types into a single chimeric protein, the vaccine elicits broader immune responses at lower doses compared to using multiple separate VLPs.
3Reliability
If VLP of one HPV type is used, then high neutralizing antibody titer is induced against that type, but cross-protection against other HPV types is low
Solution Approach 1:
The chimeric L1 protein structure incorporates specific protective epitopic regions from multiple HPV types at different locations within the single protein sequence. This local integration of foreign HPV regions maintains the overall L1 structure's ability to form proper VLPs while adding cross-reactive epitopes that induce antibodies against multiple HPV types.
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 mutated HPV58 L1 protein offers significant cross-protection against HPV58, HPV33, and HPV52, reducing the need for multiple HPV types in vaccines, thereby extending protection range and lowering production costs while maintaining effective immunogenicity.
Implementation Method 1
Major capsid protein L1 of HPV has the characteristic of self-assembling into hollow Virus-Like Particle (VLP)
Implementation Method 2
HPV VLP is highly similar to natural HPV in terms of structure, retains most of the neutralizing epitopes of natural virus, and can induce the generation of high-titer neutralizing antibodies
Data Source
AI summary
Provided are a mutated HPV58 L1 protein or a variant thereof, a sequence encoding the same, a method for preparing the same, and a virus-like particle comprising the same, wherein the protein or a variant thereof and the virus-like particle can induce the generation of neutralizing antibodies against at least two HPV types, and therefore can be used to prevent infection by said at least two HPV types, and a disease caused by said infection, such as cervical cancer and condyloma acuminatum. The invention further relates to the use of the protein and the virus-like particle in the manufacture of a pharmaceutical composition or a vaccine for preventing infection by said at least two HPV types, and a disease caused by said infection, such as cervical cancer and condyloma acuminatum.