Multi-epitopic Peptide Vaccine for Leishmaniasis

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Solution Overview

Problem

Current treatments for leishmaniasis, including chemotherapy and existing vaccines, are inadequate for asymptomatic carriers and lack a suitable human vaccine, posing challenges in effectively addressing the public health issue and economic impact of the disease.

Innovation Solution

Development of peptide compounds comprising novel epitopes from Leishmania proteins, specifically PSA, H2B, and LmLRAB proteins, designed to induce strong immunogenic responses, used in pharmaceutical compositions and vaccines to target Leishmania species, including Leishmania donovani and Leishmania infantum, with the aim of providing prophylactic and therapeutic solutions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing vaccines (CaniLeishTM, Leish-TecTM, LeishmuneTM) are used, then canine reservoir control is improved, but human vaccine coverage is insufficient and production costs are too high

Engineering Contradiction:
Improvevaccine efficacyVSAvoidproduction cost
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent extracts the essential immunogenic components (epitopes) from the complex whole Leishmania antigens used in existing vaccines. By isolating and synthesizing only the critical peptide epitopes that induce protective immunity, the invention eliminates the need for complex live attenuated organisms or whole protein preparations, thereby dramatically reducing production costs while maintaining vaccine efficacy.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the physical and chemical parameters of the vaccine from complex biological materials (live attenuated parasites or whole proteins) to simplified synthetic peptides with defined sequences. This parameter change from macromolecular complexes to small defined peptides enables cost-effective chemical synthesis and standardization, resolving the contradiction between reliability and ease of manufacture.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If single epitope vaccines are used, then production cost is reduced, but vaccine coverage and immunogenic capability are insufficient

Engineering Contradiction:
Improveproduction costVSAvoidvaccine coverage
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent merges multiple distinct epitope sequences from different Leishmania proteins into a single multi-epitopic peptide construct. This combination approach ensures broad vaccine coverage by incorporating immunodominant epitopes recognized by diverse HLA types across different Leishmania species, thereby achieving both cost-effectiveness and versatile protection.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent designs the multi-epitopic peptide to perform multiple functions simultaneously: it serves as a vaccine antigen, a diagnostic reagent, and a tool for identifying protective immune responses. The universal design incorporates conserved epitopes across Leishmania species, enabling a single vaccine formulation to provide broad-spectrum protection against diverse Leishmania strains.

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

3Ease of manufacture

If peptide derivatives of major immunogen are used, then production cost is reduced, but in vitro efficacy to stimulate human cells and produce Th1 cytokines is too low

Engineering Contradiction:
Improveproduction costVSAvoidimmunogenic capability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent optimizes the peptide sequence parameters by incorporating specific amino acid modifications, including palmitoylation at the N-terminus and optimized epitope sequences based on structural and immunological criteria. These parameter changes enhance the peptides' ability to bind to HLA molecules and stimulate robust Th1 cytokine production, resolving the contradiction between low cost and high immunogenic capability.

Inventive Principle:
Principle #35Parameter changes

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 peptide compounds demonstrate high immunogenic capability, inducing significant production of IFN-γ and activating Th1 lymphocyte-dependent cell-mediated immunity, offering a potentially effective and financially accessible vaccine solution for human populations.

Implementation Method 1

activating Th1 lymphocyte-dependent cell-mediated immunity

Methodology Applied
Scientific EffectCell-mediated immunity:

Implementation Method 2

inducing significant production of IFN-γ

Methodology Applied
Scientific EffectCytokine production:

Data Source

PatentUS11559575B2Multi-epitopic peptide compounds and vaccines against leishmaniasis
Publication Date: 2023.01.24 INSTITUT DE RES & DEV POUR LE DEVPEMENT
  • US11559575B2 patent drawing
  • US11559575B2 patent drawing
  • US11559575B2 patent drawing

AI summary

The invention relates to multi-epitopic peptide compounds obtained from PSA, HwB and LmLRAB proteins of Leishmania as well as to pharmaceutical compositions and vaccines for use against one or more leishmaniases.