Flagellin Adjuvant Enhances PAc Antigen Mucosal Immunity
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Solution Overview
Problem
Current vaccines for dental caries caused by Streptococcus mutans lack an effective mucosal immunization approach, with surface protein antigen PAc being a weak immunogen without an appropriate adjuvant, and existing adjuvants like cholera toxin are toxic and not suitable for human use.
Innovation Solution
A vaccine composition comprising a recombinant surface protein antigen PAc from Streptococcus mutans combined with flagellin as an adjuvant, administered intranasally to induce mucosal immunity, with the adjuvant enhancing antibody titers and providing protection against dental caries.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PAc antigen is administered via mucosal routes without adjuvant, then the vaccine can be safely administered, but the immunogenicity is weak and insufficient to induce effective immune response
Solution Approach 1:
The patent introduces flagellin as an intermediary adjuvant substance that mediates between the PAc antigen and the immune system. Flagellin acts as a safe mucosal adjuvant that enhances the immunogenicity of PAc antigen when administered via intranasal or oral routes, enabling effective mucosal immunity without the toxicity concerns of traditional adjuvants like cholera toxin
Solution Approach 2:
The patent changes the immunological parameters by combining PAc antigen with flagellin adjuvant in specific ratios (e.g., 1:10, 1:20, 1:50 weight ratios). This parameter optimization transforms the weak immunogenicity of pure PAc into a potent vaccine formulation that induces high titers of secretory IgA antibodies through mucosal administration
2Quantity of substance
If cholera toxin is used as adjuvant to enhance immune response, then antibody titers are improved, but toxicity increases making it unsuitable for human use
Solution Approach 1:
The patent replaces the toxic but effective cholera toxin adjuvant with flagellin, which is derived from non-toxic sources (such as Salmonella flagellin or other bacterial flagellins). This substitution maintains the adjuvant function of enhancing antibody responses while eliminating the harmful toxicity, making the vaccine suitable for human administration
Solution Approach 2:
The patent converts the potentially harmful effect of using strong adjuvants like cholera toxin into a benefit by selecting flagellin as an alternative. Flagellin naturally triggers innate immune responses through TLR5 recognition, providing the necessary adjuvant effect without the severe toxicity of cholera toxin, thus turning the search for effective adjuvants into a beneficial discovery of safe alternatives
3Ease of manufacture
If PAc is purified directly from bacterial culture, then the antigen can be obtained, but contamination cannot be ruled out and purity is in question
Solution Approach 1:
The patent extracts and purifies the PAc antigen from S. mutans bacterial culture through systematic purification procedures including cell lysis, centrifugation, and chromatography. This extraction process separates the PAc antigen from other bacterial components, ensuring high purity while maintaining the antigen's immunogenic properties for vaccine formulation
Solution Approach 2:
The patent creates a composite vaccine formulation consisting of purified PAc antigen combined with flagellin adjuvant. This composite material approach ensures both high antigen purity through separate purification and enhanced immunogenicity through the adjuvant, resolving the contradiction between ease of manufacture and manufacturing precision
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 vaccine composition effectively induces high levels of specific IgG and IgA antibodies in sera and saliva, significantly inhibiting S. mutans colonization and reducing dental caries, with flagellin acting as a potent enhancer for immune response.
Implementation Method 1
flagellin as an adjuvant, administered intranasally to induce mucosal immunity, with the adjuvant enhancing antibody titers and providing protection against dental caries
Implementation Method 2
The vaccine composition effectively induces high levels of specific IgG and IgA antibodies in sera and saliva, significantly inhibiting S. mutans colonization
Data Source
AI summary
The present invention provides a vaccine composition for dental caries caused by S. mutans infection, where the vaccine composition comprises an antigen derived from a surface protein PAc of S. mutans and an adjuvant derived from flagellin. The present invention further provides methods for preparing the vaccine composition. The present invention also provides methods for preventing or curing dental caries caused by S. mutans by administrating to a subject the vaccine composition.