Multivalent Vaccine Combinations for HPV and Hepatitis E Protection

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Solution Overview

Problem

Current HPV vaccines are type-specific and fail to offer complete protection against multiple HPV genotypes, while Hepatitis E vaccines lack cross-protection against other genotypes, and there is a need for a combination vaccine that can address high incidence and mortality rates in developing countries, particularly among pregnant women.

Innovation Solution

Development of a combination vaccine that includes HPV and Hepatitis E antigens, along with Tetanus toxoid and Tdap, formulated as a single admixture or administered concomitantly, using chimeric constructs and adjuvants like aluminum hydroxide to enhance immunogenicity and prevent antigenic interference, produced using cost-effective expression systems like Pichia pastoris.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If type-specific HPV vaccines are used, then protection against specific HPV genotypes is achieved, but complete protection against multiple HPV genotypes is not provided

Engineering Contradiction:
Improveprotection efficacyVSAvoidcoverage against multiple genotypes
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines multiple HPV antigen types (HPV16, HPV18, and other oncogenic types) into a single multivalent vaccine formulation. This merging of different antigen components allows the vaccine to provide simultaneous protection against multiple HPV genotypes, resolving the contradiction between type-specific protection and broad genotype coverage.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The vaccine formulation is designed to serve multiple protective functions against different HPV genotypes through a single administration. The multivalent composition enables universal protection across various oncogenic HPV types, eliminating the need for multiple separate vaccinations and achieving both specific and broad protection simultaneously.

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

2Adaptability or versatility

If multivalent vaccines using L1 capsid protein of at least nine HPV oncogenic viruses are used, then broad protective efficacy is achieved, but cost increases and sustainability in developing countries is compromised

Engineering Contradiction:
Improvebroad protective efficacyVSAvoidcost and sustainability
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent incorporates adjuvant components into the vaccine formulation to enhance the immunogenicity of each antigen type. By improving the local quality of the antigen-adjuvant complex, the vaccine achieves broader protective efficacy against multiple HPV genotypes without requiring increased antigen doses, thereby controlling manufacturing costs and ensuring sustainability in developing countries.

Inventive Principle:
Principle #3Local quality

3Adaptability or versatility

If HPV L1 antigens are combined with HPV L2 capsid protein, then broadly neutralizing epitopes are achieved, but immunogenicity is reduced due to poor immunogenicity of L2 protein

Engineering Contradiction:
Improvebroadly neutralizing epitopesVSAvoidimmunogenicity
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent uses L1 capsid protein as an intermediary carrier that presents L2-derived broadly neutralizing epitopes in a highly immunogenic context. The L1 protein serves as a scaffold that displays the L2 epitopes, allowing the immune system to recognize and respond to the broadly neutralizing epitopes effectively, thereby overcoming the poor immunogenicity of L2 protein while maintaining broad epitope coverage.

Inventive Principle:
Principle #24Intermediary (Mediator)

4Adaptability or versatility

If combination vaccine with multiple antigens is administered, then comprehensive protection is achieved, but antigenic interference may occur

Engineering Contradiction:
Improvecomprehensive protectionVSAvoidimmune response effectiveness
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent optimizes the formulation parameters including antigen concentrations, adjuvant ratios, and pH levels to minimize antigenic interference between multiple vaccine components. By carefully adjusting these parameters, the vaccine maintains the immunogenicity of each antigen type while achieving comprehensive protection through the combination formulation.

Inventive Principle:
Principle #35Parameter changes

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 combination vaccine provides robust antibody titers against HPV and Hepatitis E, reducing mortality and morbidity, and is cost-effective, making it suitable for widespread use in developing countries without antigenic interference.

Implementation Method 1

formulated as a single admixture or administered concomitantly, using chimeric constructs and adjuvants like aluminum hydroxide to enhance immunogenicity

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP2846829B1Vaccine combinations
Publication Date: 2021.09.08 BHARAT BIOTECH INTERNATIONAL LTD
  • EP2846829B1 patent drawingFigure 1~1B
  • EP2846829B1 patent drawingFigure 2~2B
  • EP2846829B1 patent drawingFigure 3~3B

AI summary

Vaccine combinations which comprise atleast two or more of the following antigens: DTap-HEV-HepB-HPV suitable for administration in humans. A number of variations in the combination of these antigens have been disclosed that is suitable for concomitant administration. The methods of preparing the vaccine combinations are disclosed. Nucleic acids encoding the antigens, as well as methods for their production and use are provided.