CpG-ODN Micro-Droplet Intrapulmonary Delivery for Poultry Immunity

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Solution Overview

Problem

Current methods for delivering CpG-ODN vaccines to poultry, particularly against E. coli infections, face challenges such as inefficient pulmonary delivery, rapid degradation, and the need for high dosages, which limits their effectiveness and practicality for commercial application.

Innovation Solution

A micro-droplet composition comprising immunostimulatory oligodeoxynucleotides, optionally with pharmaceutically acceptable muco-adhesive polymers, is formulated for intrapulmonary delivery using a nebulizer, allowing for effective administration and enhanced immune response in neonatal broiler chickens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CpG-ODN is administered by intramuscular or in ovo routes, then immunoprotection is achieved, but the immunogenic effect is short and practical application is limited

Engineering Contradiction:
ImproveimmunoprotectionVSAvoidimmunogenic effect duration
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent uses a pulmonary delivery system as an intermediary route to administer CpG-ODN. The respiratory tract serves as a mediator that enables prolonged immunogenic effect through sustained local immune activation and gradual systemic absorption, overcoming the short duration limitation of traditional intramuscular or in ovo routes.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the administration route parameter from intramuscular/in ovo to pulmonary delivery. This parameter change enables prolonged immunogenic effect by utilizing the respiratory tract's unique characteristics for sustained immune activation and gradual drug release, thereby extending the duration of action.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If high dosages of CpG-ODN are used, then effective immune response is achieved, but delivery efficiency and practicality are reduced

Engineering Contradiction:
Improveimmune response effectivenessVSAvoiddelivery efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The pulmonary delivery system acts as an intermediary that improves delivery efficiency. The respiratory tract serves as a conduit that enables effective immune response with reduced dosage requirements through enhanced bioavailability and targeted delivery, thereby improving productivity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the delivery parameter from traditional routes to pulmonary administration. This parameter change enhances delivery efficiency by utilizing the respiratory tract's high surface area and blood flow characteristics, enabling effective immune response with lower dosages and improved productivity.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If CpG-ODN is administered via pulmonary route, then delivery efficiency is improved, but rapid degradation occurs

Engineering Contradiction:
Improvedelivery efficiencyVSAvoidCpG-ODN stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent applies prior cushioning by formulating CpG-ODN in a stable carrier system that protects against rapid degradation before administration. The formulation includes stabilizing agents and controlled-release mechanisms that prevent premature degradation, thereby maintaining stability while preserving the delivery efficiency advantages of the pulmonary route.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

Solution Approach 2:

The patent uses composite material formulation to protect CpG-ODN from degradation. The formulation combines CpG-ODN with stabilizing carriers and protective matrices that maintain structural integrity and prevent rapid degradation, thereby preserving both delivery efficiency and compositional stability.

Inventive Principle:
Principle #40Composite materials

4Ease of operation

If traditional vaccination methods are used, then simplicity is maintained, but immune response duration and effectiveness are limited

Engineering Contradiction:
Improvevaccination simplicityVSAvoidimmune response duration
Core Design Contradiction:
Ease of operationVSDuration of action of moving object

Solution Approach 1:

The patent introduces a pulmonary delivery system as an intermediary that extends immune response duration while maintaining operational simplicity. The respiratory tract serves as a natural conduit that enables prolonged immunity through sustained local immune activation, preserving ease of operation while improving duration.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the administration parameter from traditional methods to pulmonary delivery. This parameter change extends immune response duration by utilizing the respiratory tract's unique characteristics for sustained immune activation, while maintaining the simplicity and ease of operation associated with inhalation-based delivery.

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 intrapulmonary delivery of CpG-ODN micro-droplets significantly increases survival rates and reduces bacterial counts in neonatal broiler chickens challenged with E. coli, providing prolonged immunoprotection and improved disease outcomes.

Implementation Method 1

A micro-droplet composition comprising immunostimulatory oligodeoxynucleotides, optionally with pharmaceutically acceptable muco-adhesive polymers, is formulated for intrapulmonary delivery using a nebulizer

Methodology Applied
Scientific EffectAerosolization: Aerosol

Implementation Method 2

In human and other mammalian cells, these bacterial CpG motifs or synthetic CpG-ODNs are recognized by intra-cellular toll-like receptor 9 (TLR9) present in the immune cells

Methodology Applied
Scientific EffectToll-like receptor recognition:

Implementation Method 3

CpG-ODNs induce a type 1 helper (Th1) type immune response by stimulating lymphocytes (B cells, T cells and NK cells) to secrete interleukin-6 (IL-6), interleukin-12 (IL-12) and interferon-gamma (IFN-γ)

Methodology Applied
Scientific EffectCytokine secretion:

Implementation Method 4

A micro-droplet composition comprising immunostimulatory oligodeoxynucleotides, optionally with pharmaceutically acceptable muco-adhesive polymers

Methodology Applied
Scientific EffectMucosal adhesion: Adhesive

Data Source

PatentUS11839652B2Methods and compositions for inducing protective immunity
Publication Date: 2023.12.12 UNIVERSITY OF SASKATCHEWAN
  • US11839652B2 patent drawing
  • US11839652B2 patent drawing
  • US11839652B2 patent drawing

AI summary

This application relates to compositions comprising one or more CpG oligodeoxynucleotides complexed to nanoparticles comprising a gemini surfactant and optionally a muco-adhesive polymer, which can be used for intrapulmonary delivery to induce immunity in feed animals, and the methods of making and uses thereof.