Chimeric HPV39 L1 Protein for Multi-Type Neutralizing Antibody Induction

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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 HPV39 L1 protein with specific segment substitutions from HPV68 and HPV70 proteins is developed, inducing high-titer neutralizing antibodies against multiple HPV types, providing protection comparable to a mixture of VLPs from individual HPV types at a reduced immunizing dose.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multiple HPV types are included in vaccines to broaden protection range, then the protection range is improved, but production cost and device complexity increase

Engineering Contradiction:
Improveprotection rangeVSAvoidvaccine composition complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent creates a chimeric L1 protein that combines epitopes from multiple HPV types (HPV39, HPV68, HPV70) into a single protein sequence. This single chimeric protein can induce neutralizing antibodies against multiple HPV types simultaneously, making one vaccine component perform multiple protective functions against different HPV strains.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent merges the L1 protein sequences of different HPV types by substituting specific segments (amino acid positions 269-288 and 347-358) with homologous segments from other HPV types. This merging creates a unified chimeric protein structure that retains the ability to self-assemble into VLPs while presenting multiple type-specific neutralizing epitopes.

Inventive Principle:
Principle #5Merging (Combining)

2Adaptability or versatility

If multiple HPV types are included in vaccines to broaden protection range, then the protection range is improved, but production cost increases

Engineering Contradiction:
Improveprotection rangeVSAvoidproduction cost
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The chimeric L1 protein serves as a universal vaccine component that provides protection against multiple HPV types through a single production process. By encoding all necessary epitopes from HPV39, HPV68, and HPV70 in one protein sequence, the vaccine can be manufactured as a single product rather than requiring separate production and formulation of multiple type-specific VLPs.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent combines multiple HPV type sequences into a single chimeric L1 protein that can be expressed and purified in one manufacturing batch. This merging eliminates the need for separate production lines, quality control processes, and formulation steps for each HPV type, significantly reducing manufacturing complexity and cost.

Inventive Principle:
Principle #5Merging (Combining)

3Adaptability or versatility

If multiple HPV types are included in vaccines to broaden protection range, then the protection range is improved, but safety concerns increase

Engineering Contradiction:
Improveprotection rangeVSAvoidsafety
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The chimeric L1 protein provides a safer alternative by inducing cross-protective immunity through a single immunizing agent. Instead of administering multiple type-specific VLPs that could cause cumulative immune reactions or require multiple injections, the chimeric protein delivers multiple protective epitopes in one dose, reducing the total immunizing burden and potential safety risks.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 HPV39 L1 protein offers significant cross-protection against HPV39 and other types like HPV68 and HPV70, effectively preventing infections and associated diseases such as cervical cancer and condyloma acuminatum, while reducing the complexity and cost of vaccine production.

Implementation Method 1

Major capsid protein L1 of HPV has the characteristic of self-assembling into hollow Virus-Like Particle (VLP)

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

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

Methodology Applied
Scientific EffectAntibody generation:

Data Source

PatentUS11427618B2Mutant of L1 protein of human papillomavirus type 39
Publication Date: 2022.08.30 XIAMEN INNOVAX BIOTECH
  • US11427618B2 patent drawing
  • US11427618B2 patent drawing
  • US11427618B2 patent drawing

AI summary

The invention relates to a mutated HPV39 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 (e.g. HPV39 and HPV68, or HPV39, HPV68 and HPV70), 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.