Stabilized HIV Env Trimer Vaccine Design

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Solution Overview

Problem

Current HIV vaccines face challenges in producing biochemically stable trimeric Env immunogens that elicit broadly neutralizing antibody responses, which is crucial for effective HIV vaccination.

Innovation Solution

Development of stabilized trimeric gp140 Env proteins, comprising mosaic and clade C Env polypeptides with high sequence identity, which form stable trimers to induce robust neutralizing antibody responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If traditional Env protein immunogens are used, then the vaccine structure is simpler to produce, but the biochemical stability is insufficient and fails to elicit robust neutralizing antibody responses

Engineering Contradiction:

Improvebiochemical stability of trimeric Env immunogenVSAvoiddifficulty in producing stable trimeric structure

Core Design Contradiction:

Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The patent modifies the Env protein sequence by introducing mutations in the gp41 region (specifically the I559L, V562I, and G566S mutations) to enhance trimer stability. These parameter changes in the amino acid sequence improve the biochemical stability of the trimeric structure while maintaining its immunogenicity and ability to elicit neutralizing antibody responses

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite trimeric structure by combining mosaic Env polypeptides (comprising sequences from multiple HIV clades) with stabilized gp41 regions. This composite approach integrates diverse viral sequences to broaden immune recognition while the stabilized gp41 core ensures structural integrity and resistance to dissociation

Inventive Principle:

Principle #40Composite materials

2Reliability

If the Env trimer structure is stabilized through mutations, then the neutralizing antibody response is enhanced, but the sequence complexity increases

Engineering Contradiction:

Improveefficacy in eliciting neutralizing antibody responsesVSAvoidsequence complexity of mosaic Env polypeptides

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the Env protein into distinct functional segments: the gp120 region (amino acids 1-545) which contains the variable neutralization epitopes, and the gp41 region (amino acids 550-724) which provides the stabilized trimeric core. This segmentation allows the variable gp120 portions to elicit broad neutralizing antibodies while the standardized gp41 portion ensures structural stability and proper folding

Inventive Principle:

Principle #1Segmentation

Data Source

PatentEP2983686B1Stabilized human immunodeficiency virus (HIV) envelope (ENV) trimer vaccines and methods of using the same

Publication Date: 2024.05.29 BETH ISRAEL DEACONESS MEDICAL CENT INC

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AI summary

The invention features stabilized human immunodeficiency virus (HIV) envelope (Env) trimers. The invention also features vaccines, nucleic acids, and vectors to deliver and/or facilitate production of the stabilized HIV Env trimers. In addition, the invention features methods of making and using the stabilized HIV Env trimers of the invention as vaccines.