Optimized HIV EnvF Gene Expression in Vaccine Vectors

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Solution Overview

Problem

Existing vaccine delivery vectors face challenges such as poor foreign protein expression, inefficient post-translational processing, and gene insert instability, particularly when encoding HIV proteins, due to cytotoxicity and replicative fitness issues associated with nucleotide sequences and encoded proteins.

Innovation Solution

Development of optimized HIV immunogens, specifically Env-F hybrids based on BG505, for use in negative-strand RNA virus vectors and plasmid DNA vectors, which include signal peptide and transmembrane domain modifications to enhance expression and stability, utilizing Vero cells and electroporation-based rescue methods to generate recombinant viral vectors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If HIV envelope gene is expressed in vaccine delivery vectors, then immunogenicity is improved, but cytotoxicity increases and replicative fitness decreases

Engineering Contradiction:

ImproveimmunogenicityVSAvoidcytotoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by optimizing the nucleotide sequence of the HIV envelope gene through codon usage optimization and removing cytotoxic sequences. This modifies the genetic parameters to reduce cytotoxicity while preserving immunogenicity, allowing the gene to be safely expressed in vaccine vectors without killing host cells or compromising vaccine effectiveness.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent extracts and removes cytotoxic sequences from the HIV envelope gene that would otherwise harm the host cells. By identifying and eliminating these harmful sequence elements, the invention separates the immunogenic properties from the cytotoxic properties, allowing safe expression in vaccine delivery systems.

Inventive Principle:

Principle #2Taking out (Extraction)

2Reliability

If HIV envelope gene is expressed in vaccine delivery vectors, then immunogenicity is improved, but gene insert instability increases

Engineering Contradiction:

ImproveimmunogenicityVSAvoidgene insert stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the nucleotide sequence parameters of the HIV envelope gene to match the codon usage preferences of the host cell. This optimization stabilizes the gene insert by making it more compatible with the host's transcriptional and translational machinery, preventing gene silencing or loss during vaccine vector propagation while maintaining immunogenicity.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If HIV envelope gene is expressed in vaccine delivery vectors, then antigenicity is improved, but foreign protein expression efficiency decreases

Engineering Contradiction:

ImproveantigenicityVSAvoidforeign protein expression efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent optimizes the HIV envelope gene's nucleotide sequence by adjusting codon usage to match host cell preferences and improving mRNA stability. These parameter changes enhance the efficiency of foreign protein expression in vaccine vectors, ensuring high levels of antigen production while maintaining the immunogenic and antigenic properties of the HIV envelope protein.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS10792357B2Optimized HIV envelope gene and expression thereof

Publication Date: 2020.10.06 INTERNATIONAL AIDS VACCINE INITIATIVE INC

AI summary

The present invention relates to a vector(s) containing and expressing an optimized HIV EnvF gene, methods for making the same and cell substrates qualified for vaccine production which may comprise vector(s) containing optimized HIV genes.