Avian Immunostimulatory Compositions for TLR21 Activation

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Solution Overview

Problem

Existing immunostimulatory compositions fail to elicit sufficient non-specific immune responses against pathogens, particularly in large-scale animal production, and there is a need for alternatives to antibiotic treatment due to antibiotic resistance and consumer demand for antibiotic-free animal products.

Innovation Solution

Immunostimulatory compositions comprising an immunomodulator composition with a non-coding nucleic acid plasmid and a cationic lipid delivery vehicle, combined with an immunostimulatory oligonucleotide having a CpG motif and a guanine nucleotide-enriched sequence at the 5' terminus, are administered to stimulate TLR21 and elicit an immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If administered immunostimulatory plasmids or oligonucleotides alone, then TLR21 activation occurs, but the immune response is insufficient to combat infection

Engineering Contradiction:

Improveimmune response efficacyVSAvoidcomposition complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines immunostimulatory oligonucleotides with immunomodulator compositions containing cationic lipids and non-coding nucleic acid plasmids to create a composite formulation. This composite approach enhances TLR21 activation and produces a synergistic immune response that is greater than the sum of individual components, thereby resolving the insufficiency of single-component administrations.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent introduces cationic lipids as intermediary delivery vehicles that facilitate the uptake and cellular internalization of immunostimulatory oligonucleotides. These lipids act as mediators that enhance the interaction between the oligonucleotides and target cells, improving the reliability of immune response activation without requiring complex delivery systems.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If antibiotics are administered prophylactically to large populations, then infection resistance increases, but antibiotic resistance emerges

Engineering Contradiction:

Improveinfection resistanceVSAvoidantibiotic resistance

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful overreliance on antibiotics into a beneficial alternative by utilizing the animal's own immune system. By administering immunostimulatory compositions that activate TLR21 and enhance non-specific immune responses, the treatment provides infection resistance through immune activation rather than direct antimicrobial action, thereby eliminating the selection pressure that drives antibiotic resistance.

Inventive Principle:

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

Solution Approach 2:

The patent enables the animal's immune system to serve itself by providing immunostimulatory compositions that activate endogenous immune pathways. The oligonucleotides with CpG motifs and guanine-rich sequences trigger the animal's own TLR21-mediated immune responses, creating a self-sustaining defense mechanism that does not require continuous antibiotic intervention.

Inventive Principle:

Principle #25Self-service

3Reliability

If immunostimulatory oligonucleotides with CpG motifs are administered, then TLR21 activation occurs, but response sufficiency is inadequate

Engineering Contradiction:

Improveimmune response activationVSAvoidimmune response magnitude

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent merges immunostimulatory oligonucleotides with immunomodulator compositions in a single administered formulation. This combination merges the TLR21 activation capability of CpG-containing oligonucleotides with the immune-enhancing properties of cationic lipids and non-coding plasmids, producing a synergistic effect that amplifies the magnitude of the immune response beyond what either component achieves alone.

Inventive Principle:

Principle #5Merging (Combining)

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 compositions effectively stimulate TLR21-mediated immune responses, providing a non-specific defense against pathogens and reducing the reliance on antibiotics in animal production.

Implementation Method 1

an immunomodulator composition comprising an immunogenic nucleic acid plasmid and a liposomal delivery vehicle

Methodology Applied

Scientific EffectCationic lipid delivery:

Implementation Method 2

toll-like receptor protein 21 (TLR21) is the chicken functional homolog of mammalian TLR9 and is capable of recognizing unmethylated CpG motifs

Methodology Applied

Scientific EffectToll-like receptor recognition:

Implementation Method 3

activation of TLR21 by CpG motif-containing nucleic acids has been shown to activate cellular signals involved in the immune responses to microbial infections

Methodology Applied

Scientific EffectCellular signaling activation:

Implementation Method 4

centrifuging the immunostimulatory composition to generate a supernatant and a pellet

Methodology Applied

Scientific EffectCentrifugation: Centrifuge

Data Source

PatentEP3700564B1Immunostimulatory compositions

Publication Date: 2025.09.17 ELANCO ANIMAL HEALTH GMBH

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AI summary

The present disclosure relates to immunostimulatory compositions that are effective in eliciting immune responses in avian species. More specifically, these immunostimulatory compositions comprise an immunomodulator composition and an immunostimulatory oligonucleotide that when administered stimulate toll-like receptor 21.