Hyr1 Polypeptide Fragments for Candida and Acinetobacter Immunotherapy

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Solution Overview

Problem

Current antifungal therapies for Candida infections are inadequate due to high mortality rates and toxicity issues, and there is a lack of effective prevention methods for infections caused by antibiotic-resistant bacteria like Acinetobacter species.

Innovation Solution

Development of immunotherapeutic approaches using fragments of the Candida cell surface protein Hyr1 and Acinetobacter proteins to create vaccines and antibodies that provide immunity against Candida and Acinetobacter infections, including the use of polypeptides, conjugates, and recombinant fusion proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional antifungal agents such as amphotericin B are used to treat Candida infections, then microbial killing effectiveness is improved, but toxicity and mortality remain problematic

Engineering Contradiction:
Improvemicrobial killing effectivenessVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces antibodies as intermediary molecules that mediate the killing of Candida cells. These antibodies bind to specific antigens on the Candida cell surface and facilitate phagocytic killing by macrophages, serving as a biological intermediary that transfers the killing function from direct antifungal chemicals to an immune-mediated process, thereby reducing toxicity while maintaining effectiveness

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the chemical-microbial interaction mechanism with an immune-based mechanism. Instead of using chemical antifungals that directly kill Candida cells through membrane disruption, the invention uses antibodies to trigger phagocytic killing, substituting the chemical action mechanism with an immunological one that is more selective and less toxic to host tissues

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Object-affected harmful factors

If passive or active immunotherapy is used to treat disseminated candidiasis, then toxicity is reduced, but effectiveness must be proven superior to existing antifungals

Engineering Contradiction:
ImprovetoxicityVSAvoidtreatment effectiveness
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent employs feedback mechanisms through the use of specific antibody-antigen interactions. The antibodies are designed to bind with high affinity to specific Candida antigens, creating a feedback loop where the antibody binding triggers phagocytic killing. This feedback mechanism ensures that the immune response is targeted and effective, providing evidence of superior effectiveness compared to non-specific antifungals

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent changes the parameter of treatment specificity from non-specific antifungal action to specific antigen-targeted immunity. By focusing the immune response on specific Candida antigens through monoclonal or polyclonal antibodies, the system achieves higher specificity and potentially greater effectiveness while maintaining lower toxicity, representing a fundamental parameter change in the approach to antifungal therapy

Inventive Principle:
Principle #35Parameter changes

3Reliability

If immunotherapeutic approaches using Hyr1 fragments are developed, then immunity against Candida and Acinetobacter is achieved, but development complexity increases

Engineering Contradiction:
Improveimmunity effectivenessVSAvoidvaccine development complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by using fragments of the Hyr1 protein rather than the complete protein for vaccine development. These peptide fragments (such as sequences comprising amino acids 1-20, 21-40, or specific epitopes) retain immunogenicity while being easier to produce, purify, and formulate, thereby reducing the complexity of vaccine development while maintaining effectiveness

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent demonstrates universality by showing that Hyr1 protein fragments elicit immune responses that provide protection against both Candida albicans and Acinetobacter baumannii infections. This multi-functional capability of a single antigenic target reduces the need for separate vaccines for different pathogens, simplifying the overall development strategy and reducing complexity through cross-protection

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 approach significantly reduces the risk and severity of infections by eliciting an immune response, offering a potentially more effective and less toxic alternative to traditional antifungal treatments and addressing the challenge of antibiotic-resistant bacteria.

Implementation Method 1

fragments of the Candida cell surface protein Hyr1 are useful in immunizing a subject against Candida infections

Methodology Applied
Scientific EffectImmune response:

Implementation Method 2

The identification of effectors in the regulatory pathways of the organism that contribute to virulence offers the opportunity for therapeutic intervention

Methodology Applied
Scientific EffectAntibody binding:

Implementation Method 3

The primary host defense mechanism against disseminated candidiasis is phagocytic killing of the organism. Only phagocytic cells are capable of directly killing Candida in vitro

Methodology Applied
Scientific EffectPhagocytic killing:

Implementation Method 4

active immunotherapy to treat or prevent disseminated candidiasis is a promising alternative to standard antifungal therapy

Methodology Applied
Scientific EffectImmune-mediated destruction:

Data Source

PatentUS10160790B2HYR1-derived compositions and methods of treatment using same
Publication Date: 2018.12.25 LOS ANGELES BIOMEDICAL RES INST AT HARBOR UCLA MEDICAL CENT
  • US10160790B2 patent drawing
  • US10160790B2 patent drawing
  • US10160790B2 patent drawing

AI summary

The disclosure features isolated polypeptides of Hyr1. The disclosure further features vaccines and antibodies useful in treating or preventing candidiasis or Acinetobacter infections or both. Further disclosed are isolated polypeptides consisting of between 14 and 20 amino acids for vaccine preparation. The specific amino acid sequences of isolated polypeptides of Hyr1 are also disclosed.