Therapeutic HPV16 Vaccine Using Re-ordered E6 E7 Peptides

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Solution Overview

Problem

Current therapeutic vaccines for human papillomavirus type 16 (HPV16) are limited by their ability to address established genital lesions and cancer, with existing approaches showing limited efficacy and adverse effects, and there is a need for vaccines that can effectively induce an immune response without oncogenic potential.

Innovation Solution

Nucleic acid molecules encoding polypeptides that comprise re-ordered fragments of HPV16 E6 and E7 proteins, minimizing transforming activity and undesired epitopes, while including all possible T-cell epitopes, are used to develop a vaccine that can induce an immune response against HPV16, potentially combined with HPV16 E2 protein mutations to reduce DNA binding activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If wild-type E6 and E7 proteins are used in therapeutic vaccines, then strong immune response is induced, but oncogenic transformation risk increases

Engineering Contradiction:

Improveimmune response efficacyVSAvoidoncogenic transformation risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The E6 and E7 proteins are divided into multiple peptide fragments or epitopes. Instead of using the complete wild-type proteins, the invention employs segmented peptide representations that retain immunogenicity while eliminating oncogenic sequences. This segmentation allows the vaccine to stimulate immune response without introducing transformative activity.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Specific oncogenic regions or transforming domains are extracted and removed from the E6 and E7 protein sequences. The vaccine composition includes only the immunogenic epitopes necessary for immune recognition, while deliberately excluding the portions responsible for oncogenic transformation. This extraction process maintains therapeutic efficacy while eliminating harmful effects.

Inventive Principle:

Principle #2Taking out (Extraction)

2Adaptability or versatility

If complete E6 and E7 protein sequences are used, then all T-cell epitopes are included, but manufacturing complexity and safety concerns increase

Engineering Contradiction:

Improveepitope coverageVSAvoidmanufacturing and safety complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

Instead of including the complete E6 and E7 protein sequences, the invention uses a curated selection of partial sequences that cover all essential T-cell epitopes. This partial action approach provides sufficient immunogenic coverage without the unnecessary complexity and safety risks associated with complete protein sequences. The vaccine includes exactly what is needed—no more, no less.

Inventive Principle:

Principle #16Partial or excessive action

3Ease of operation

If traditional therapeutic vaccine approaches are used for established HPV lesions, then treatment options are available, but efficacy is limited and adverse effects occur

Engineering Contradiction:

Improvetreatment availabilityVSAvoidclinical efficacy

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The vaccine employs a composite composition of multiple peptide fragments from E6 and E7, potentially combined with adjuvants and delivery system components. This composite approach enhances immunogenicity and clinical efficacy compared to single-component traditional vaccines. The composite structure allows optimization of both safety and effectiveness for treating established HPV lesions.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS11040096B2Therapeutic HPV16 vaccines

Publication Date: 2021.06.22 VIDAMUNE BV

AI summary

Provided is designer nucleic acid constructs and polypeptides that can be used as therapeutic vaccines against HPV16.