Immunogenic Polypeptides for HIV T Cell Response

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for treating HIV infection are inadequate, as HIV has developed proteins that antagonize endogenous anti-viral proteins, leading to ineffective proteolytic degradation and immune response suppression.

Innovation Solution

Development of isolated polypeptides with substantial amino acid sequence identity to endogenous anti-viral polypeptides, such as APOBEC, tetherin, and TRIM5, which are subject to viral protein-mediated proteolytic degradation, used in immunogenic compositions to stimulate specific T cell responses and enhance immune recognition of retrovirus-infected cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If HIV viral proteins (Vif, Vpu) are present to antagonize endogenous anti-viral proteins, then viral replication is enhanced, but endogenous anti-viral protein activity is suppressed through proteolytic degradation

Engineering Contradiction:

Improveanti-viral protein activityVSAvoidproteolytic degradation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary action by pre-identifying and characterizing the specific peptide sequences of endogenous anti-viral proteins (APOBEC3G, tetherin, TRIM5) before viral infection occurs. This allows for the development of vaccines and therapeutics that target these proteins' epitopes, enabling the immune system to recognize and respond to viral proteins that cause proteolytic degradation before the virus can suppress anti-viral activity

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent converts the harmful effect of viral proteins into a beneficial immune response by using the viral proteins themselves (Vif, Vpu) as antigens in vaccine formulations. The immune system is trained to recognize these viral proteins that cause proteolytic degradation, transforming the harmful viral factors into targets for protective immunity

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Reliability

If current HIV treatment methods are used, then some viral replication is controlled, but treatment effectiveness is insufficient due to viral protein antagonism

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidviral protein antagonism

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies universality by developing a multi-component vaccine formulation that includes multiple endogenous anti-viral protein peptides (APOBEC3G, tetherin, TRIM5) and their viral antagonists (Vif, Vpu). This multi-functional approach targets several viral mechanisms simultaneously, making it harder for the virus to evade treatment through single-point mutations or antagonism

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent applies parameter changes by modifying the immunogenicity parameters of the vaccine formulation through the use of adjuvants and optimized peptide sequences. This enhances the immune response to endogenous anti-viral proteins, changing the threshold at which protective immunity is achieved and overcoming the suppressive effects of viral protein antagonism

Inventive Principle:

Principle #35Parameter changes

3Reliability

If isolated polypeptides with substantial amino acid sequence identity to endogenous anti-viral polypeptides are used, then T cell response is enhanced, but complexity of immunogenic composition increases

Engineering Contradiction:

ImproveT cell responseVSAvoidimmunogenic composition

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the endogenous anti-viral proteins into smaller peptide segments or epitopes (e.g., specific amino acid sequences from APOBEC3G, tetherin, TRIM5). This segmentation makes the proteins more manageable for vaccine formulation while preserving the immunogenic regions that elicit protective T cell responses, reducing the complexity of delivering full-length proteins

Inventive Principle:

Principle #1Segmentation

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 immunogenic compositions induce robust T cell responses, including CD4+ and CD8+ T cell activation and cytokine secretion, effectively targeting retrovirus-infected cells and potentially improving HIV treatment and prophylaxis outcomes.

Implementation Method 1

endogenous anti-viral polypeptides are polypeptides subject to proteolytic degradation as a result of the activity of one or more viral proteins

Methodology Applied

Scientific EffectProteolytic degradation: Decomposition (biological)

Implementation Method 2

immunogenic compositions comprising a subject isolated polypeptide... induce robust T cell responses, including CD4+ and CD8+ T cell activation and cytokine secretion

Methodology Applied

Scientific EffectAntigen recognition:

Data Source

PatentUS9572873B2Method of inducing a T lymphocyte response using T-cell immunogens derived from anti-viral proteins

Publication Date: 2017.02.21 RGT UNIV OF CALIFORNIA

AI summary

Isolated polypeptides related to endogenous anti-viral polypeptides; and compositions, including immunogenic compositions, comprising a subject isolated polypeptide are disclosed herein. A subject isolated polypeptide comprises an amino acid sequence having substantial amino acid sequence identity to a contiguous stretch of amino acids of one or more endogenous anti-viral polypeptides, wherein the endogenous anti-viral polypeptides are polypeptides subject to proteolytic degradation as a result of the activity of one or more viral proteins. Also provided are diagnostic and treatment methods using the subject isolated polypeptides and compositions.