Yeast Surface Display Edible Vaccine for Hepatitis B

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Solution Overview

Problem

Current HBV vaccines are ineffective in treating existing infections and are not suitable for low-income populations due to injectable administration, with no commercial oral administration options available, and existing yeast surface display systems have limitations in producing edible vaccines.

Innovation Solution

Development of a yeast surface display system using Saccharomyces cerevisiae to express HBsAg proteins on the surface of yeast, followed by lyophilization and encapsulation for oral administration, with antibody responses detected via ELISA, to create an edible vaccine for preventive and therapeutic HBV treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional injection-based HBV vaccines are used, then immune protection is achieved, but ease of operation deteriorates due to requiring trained personnel and injection equipment

Engineering Contradiction:
Improveimmune protectionVSAvoidadministration convenience
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent replaces the mechanical injection system with an oral administration system. The vaccine is delivered via yeast cells that can be orally ingested, eliminating the need for syringes, needles, and trained injection personnel. The yeast surface display system presents HBsAg antigens that are naturally taken up by the immune system through the oral route, substituting mechanical delivery with a biological delivery mechanism.

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

2Productivity

If P.pastoris secretion system is used to produce HBV vaccines, then vaccine production is achieved, but adaptability deteriorates because it cannot produce edible vaccines for oral administration

Engineering Contradiction:
Improvevaccine productionVSAvoidoral administration capability
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent employs S.cerevisiae yeast surface display system that serves multiple functions: it can produce HBsAg antigens for both preventive and therapeutic vaccines, and the same system can be adapted for oral administration. The yeast surface display technology allows the antigen to be presented on the cell surface in a native-like conformation, making it suitable for oral delivery while maintaining immunogenicity.

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

3Ease of operation

If edible vaccines are developed using yeast surface display, then ease of operation improves for oral administration, but manufacturing precision deteriorates due to challenges in maintaining antigen stability and expression

Engineering Contradiction:
Improveoral administrationVSAvoidantigen stability
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent optimizes several parameters to maintain antigen stability: the yeast strain is selected and conditioned for optimal growth and antigen expression; cultivation conditions (temperature, pH, nutrients) are controlled to ensure consistent antigen presentation on yeast surfaces; the yeast cells are formulated with protective excipients and encapsulated to maintain antigen stability during storage and oral passage through the gastrointestinal tract.

Inventive Principle:
Principle #35Parameter changes

4Adaptability or versatility

If conventional HBV vaccines are used, then prevention of HBV infection is achieved, but adaptability deteriorates as there is no cure for existing infections

Engineering Contradiction:
Improvetherapeutic capabilityVSAvoidinfection prevention
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The yeast surface display vaccine system is designed to be universally applicable for both prevention and treatment. The system can present multiple HBV antigens (surface antigens and core antigens) simultaneously or separately, enabling it to function as a preventive vaccine for naïve individuals and as a therapeutic vaccine for chronically infected patients. The oral delivery route enhances mucosal immunity which is particularly valuable for therapeutic applications.

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 yeast surface display system effectively induces antibody responses, providing immune protection against HBV infection and potentially treating existing infections, while offering a cost-effective and non-perishable oral vaccine solution.

Implementation Method 1

a N-terminal display plasmid, pYD5, to display preS2/S (adw) or preS2/S (adr) protein on the surface of S.cerevisiae EBY100

Methodology Applied
Scientific EffectYeast surface display:

Implementation Method 2

The recombinant yeast after lyophilization is encapsulated by enteric capsule

Methodology Applied
Scientific EffectLyophilization: Freeze Drying

Implementation Method 3

The recombinant yeast after lyophilization is encapsulated by enteric capsule

Methodology Applied
Scientific EffectEncapsulation:

Implementation Method 4

followed by ELISA detecting antibody responses

Methodology Applied
Scientific EffectELISA: Absorption Spectroscopy

Data Source

PatentUS10793866B2Edible vaccines expressed in yeast for preventing and treating infectious diseases, including hepatitis B, in humans
Publication Date: 2020.10.06 DRD IMMUNETECH INT LTD

AI summary

In the invention described here, the approach is to formulate an edible vaccine based on N-terminal yeast surface display expression platform that producing S.cerevisiae EBY100/pYD5-preS2/S(adw) and S.cerevisiae EBY100/pYD5-preS2/S(adr) for protecting and treating human against hepatitis B virus (HBV) infection, suggesting that yeast surface display expression system expressing HBsAg antigen has potential as a prophylactic treatment for HBV in human via oral vaccination. The technology developed in this patent application can also be used to produce edible (oral) vaccines for preventing and treating other infectious diseases in human.