Trimeric gp120 Vaccine Composition for Native-Like HIV Antigens
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Solution Overview
Problem
Current immunization strategies against HIV-1 have been unsuccessful in generating broadly neutralizing antibodies, and existing recombinant HIV proteins often mis-fold, failing to preserve native conformation and evoke effective immune responses.
Innovation Solution
Development of recombinant subunit vaccines comprising an ecto-domain of HIV gp120 protein fused in-frame to a C-propeptide of collagen, forming disulfide bond-linked trimers, which are expressed and purified to maintain native-like conformation, thereby promoting robust immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If recombinant HIV proteins are expressed in soluble forms without transmembrane and cytoplasmic domains, then expression and purification become easier, but the viral antigens mis-fold and fail to preserve native conformation
Solution Approach 1:
The patent introduces a collagen C-propeptide as an intermediary trimerization domain that mediates the formation of stable trimers by the soluble gp120 ectodomains. This intermediary element enables the soluble proteins to self-assemble into trimeric structures that preserve native conformation, resolving the contradiction between ease of manufacture and manufacturing precision
Solution Approach 2:
The patent creates a composite structure by fusing the HIV gp120 ectodomain with the collagen C-propeptide domain. This composite recombinant protein combines the antigenic properties of gp120 with the structural stability and trimerization capability of collagen, achieving both ease of expression and native-like conformation
2Device complexity
If recombinant HIV proteins are expressed as monomers, then production is simpler, but they fail to evoke neutralizing antibodies
Solution Approach 1:
The patent merges multiple gp120 monomers into a trimeric structure through the collagen C-propeptide domain. This merging of three monomeric units into a functional trimer restores the native quaternary structure, enabling the protein to evoke neutralizing antibodies while maintaining relatively simple production requirements
3Productivity
If mis-folded viral antigens are used in vaccines, then production cost is reduced, but they fail to generate broadly neutralizing antibodies
Solution Approach 1:
The patent changes the structural parameters of the recombinant protein by introducing the collagen C-propeptide domain, which fundamentally alters the folding behavior and quaternary structure. This parameter change enables the protein to maintain stable, native-like conformation during production, thereby generating broadly neutralizing antibodies while preserving production efficiency
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 recombinant subunit vaccines induce neutralizing antibodies against diverse HIV strains, including Tier 2 viruses, and avoid antibody-dependent enhancement, providing a safer and more effective immunization approach.
Implementation Method 1
the C-terminal propeptides form inter-polypeptide disulfide bonds
Data Source
AI summary
The present invention discloses immunogenic compositions including recombinant peptides and proteins comprising human immunodeficiency viruses (HIV) antigens and immunogens, e.g., gp 120 protein peptides. In some aspects, the immunogenic composition comprises a secreted fusion protein comprising a soluble HIV viral antigen joined by in-frame fusion to a C-terminal portion of a collagen which is capable of self-trimerization to form a disulfide bond-linked trimeric fusion protein. In some aspects, the immunogenic compositions provided herein are useful for generating an immune response, e.g., for treating or preventing an HIV infection. In some aspects, the immunogenic compositions provided herein may be used in a vaccine composition, e.g., as part of a prophylactic and/or therapeutic vaccine. Also provided herein are methods for producing the recombinant peptides and proteins, prophylactic, therapeutic, and/or diagnostic methods, and related kits.