Pulsatile Vaccine Formulations for Single-Injection Booster Release

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Solution Overview

Problem

Existing vaccine delivery systems require multiple doses due to lack of effective methods for controlled, sustained release of antigens, which increases costs and practicality issues, especially in developing countries, and pose challenges in stabilizing encapsulated antigens during storage and administration.

Innovation Solution

Development of injectable polymeric formulations using biocompatible, biodegradable polymers like PLGA, formulated through micromolding or 3D printing, which provide discrete antigen release at multiple time periods, stabilized by trehalose glass, and minimize antigen damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If multiple booster doses are administered to achieve effective vaccination, then immune response reliability is improved, but vaccination complexity and cost increase

Engineering Contradiction:

Improveimmune response reliabilityVSAvoidvaccination complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The vaccine formulation is segmented into multiple functional components: antigen, adjuvant, and stabilizer, each encapsulated within biodegradable polymer microspheres. This segmentation allows each component to be released at optimized rates, with the antigen providing sustained release over months, thereby eliminating the need for multiple booster doses while maintaining reliable immune response.

Inventive Principle:

Principle #1Segmentation

2Stability of the object's composition

If refrigerated storage is implemented to maintain vaccine stability, then antigen stability is improved, but distribution cost and complexity increase

Engineering Contradiction:

Improveantigen stabilityVSAvoiddistribution cost

Core Design Contradiction:

Stability of the object's compositionVSUse of energy by stationary object

Solution Approach 1:

The patent employs inexpensive, non-refrigerated stabilizing agents such as sugars (sucrose, trehalose), amino acids, and polyols that can be easily incorporated into the vaccine formulation. These stabilizers protect the antigen during storage at ambient temperatures without requiring expensive refrigeration infrastructure, making the vaccine suitable for distribution in developing countries.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Speed

If rapid antigen release occurs to induce immediate immune response, then immune response speed is improved, but antigen depletion rate increases requiring booster doses

Engineering Contradiction:

Improveimmune response speedVSAvoidantigen release duration

Core Design Contradiction:

SpeedVSDuration of action of moving object

Solution Approach 1:

The vaccine formulation implements periodic antigen release through the controlled degradation of biodegradable polymer microspheres. The release occurs in phases: an initial burst release provides immediate immune stimulation, followed by sustained release over several months as the polymer degrades. This periodic action maintains adequate antigen levels continuously, eliminating the need for booster doses.

Inventive Principle:

Principle #19Periodic action

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

Achieves stable, controlled release of antigens at multiple times, reducing the need for booster doses and enhancing immune response, suitable for subcutaneous, intramuscular, or mucosal administration, and applicable for various therapeutic, prophylactic, and diagnostic agents.

Implementation Method 1

The potency of these optimal depot formulations for antigen may be enhanced by the co-delivery of vaccine adjuvants, including cytokines, that are either entrapped in the polymer matrix or, alternatively, incorporated into the backbone of the polymer itself and released concomitantly with antigen as the polymer degrades.

Methodology Applied

Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

Antigen may be stabilized through the use of stabilizing agents such as trehalose glass.

Methodology Applied

Scientific EffectVitrification: Vitrification

Data Source

PatentUS12622963B2Micromolded or 3-D printed pulsatile release vaccine formulations

Publication Date: 2026.05.12 TOKITAE LLC

AI summary

Emulsion-based and micromolded (“MM”) or three dimensional printed (“3DP”) polymeric formulations for single injection of antigen, preferably releasing at two or more time periods, have been developed. Formulations are preferably formed of biocompatible, biodegradable polymers. Discrete regions encapsulating antigen, alone or in combination with other antigens, adjuvants, stabilizers, and release modifiers, are present in the formulations. Antigen is preferably present in excipient at the time of administration, or on the surface of the formulation, for immediate release, and incorporated within the formulation for release at ten to 45 days after initial release of antigen, optionally at ten to 90 day intervals for release of antigen in one or more additional time periods. Antigen may be stabilized through the use of stabilizing agents such as trehalose glass. In a preferred embodiment for immunization against polio, antigen is released at the time of administration, and two, four and six months thereafter.