HPV11 L1 Protein C-Terminus Modification for Expression Yield

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Solution Overview

Problem

Current HPV vaccines face challenges in achieving high expression levels and purification yields of HPV L1 proteins, particularly for HPV11, which affects the induction of neutralizing antibodies and the overall efficacy of the vaccine.

Innovation Solution

C-terminus modification of the HPV11 L1 protein by substituting basic amino acids with polar, non-polar, or acidic amino acids increases expression levels and assembly efficiency, leading to the formation of virus-like particles that induce a protective immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional HPV L1 protein expression systems are used, then vaccine production can be maintained, but expression levels and purification yields are insufficient, particularly for HPV11

Engineering Contradiction:

Improveexpression level of HPV11 L1 proteinVSAvoidpurification yield of L1VLP

Core Design Contradiction:

Quantity of substanceVSProductivity

Solution Approach 1:

The patent applies parameter changes by modifying the C-terminus amino acid sequence of the HPV11 L1 protein. Specifically, basic amino acids at the C-terminus are replaced with polar, non-polar, or acidic amino acids to alter the protein's expression level and assembly properties in insect cell expression systems, thereby resolving the contradiction between expression level and purification yield

Inventive Principle:

Principle #35Parameter changes

2Reliability

If standard HPV L1 protein sequences are used, then vaccine formulation is straightforward, but neutralizing antibody induction is insufficient

Engineering Contradiction:

Improveinduction of neutralizing antibodiesVSAvoidvaccine efficacy

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies local quality by making targeted modifications only at the C-terminus region of the HPV11 L1 protein while maintaining the rest of the protein sequence intact. This localized modification at the C-terminus enhances the protein's ability to induce neutralizing antibodies without compromising the overall vaccine formulation and manufacturing process

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20240000915A1C-terminally modified human papillomavirus type 11 l1 protein and use thereof

Publication Date: 2024.01.04 INSTITUTE OF BASIC MEDICAL SCIENCES CHINESE ACADEMY OF MEDICAL SCIENCES

AI summary

The present application relates to a C-terminus modified human papillomavirus type 11 L1 protein and the use thereof. Specifically, the present application relates to a C-terminus modified human papillomavirus (HPV) type 11 L1 protein, a nucleotide encoded thereby, a vector containing the nucleotide, a cell containing the vector, a pentamer or virus-like particle composed of the HPV11 L1 protein, and a vaccine containing the pentamer or virus-like particle and a vaccine adjuvant, and the use thereof in the prevention of HPV infection and HPV infection-related diseases.