Chimeric FhbB Vaccine Blocks Factor H Binding
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for periodontal disease are expensive, invasive, and inaccessible to many, and there is a need for effective agents that can protect against the pathogenesis of Treponema denticola, which contributes to the disease through its Factor H Binding Protein B (FhbB) that binds to Factor H, leading to immune dysregulation.
Innovation Solution
Development of recombinant chimeric polypeptides comprising genetically engineered mutants of T. denticola FhbB proteins that no longer bind to Factor H, administered to elicit antibody production, which blocks T. denticola's ability to bind to Factor H, leading to antibody-mediated killing of the bacteria.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for periodontal disease are used, then disease progression can be managed, but treatment cost and invasiveness increase significantly
Solution Approach 1:
The patent employs a vaccine-based preventive approach using recombinant FhbB proteins that can be administered systemically to provide long-term protective immunity against T. denticola, replacing the need for repeated expensive and invasive treatments
Solution Approach 2:
The vaccine induces pre-existing immunity before infection or disease progression occurs, allowing the immune system to neutralize T. denticola upon exposure, thereby preventing disease development rather than treating established conditions
2Reliability
If T. denticola binds to Factor H via FhbB, then bacterial survival and immune evasion are enhanced, but immune dysregulation and disease progression occur
Solution Approach 1:
The patent exploits the FhbB-Factor H interaction as a target for intervention. By designing recombinant FhbB proteins that compete for Factor H binding or induce neutralizing antibodies, the harmful bacterial attachment mechanism is converted into a beneficial therapeutic target that prevents immune evasion when blocked by antibodies
Solution Approach 2:
The recombinant FhbB proteins act as intermediaries that bind to Factor H with high affinity, preventing T. denticola from accessing Factor H. These soluble FhbB proteins serve as decoys that intercept the bacterial-pathway interaction, neutralizing the harmful effect without requiring direct contact with the bacteria
3Reliability
If recombinant chimeric polypeptides are developed to block FhbB-Factor H binding, then antibody-mediated bacterial killing is achieved, but vaccine development complexity increases
Solution Approach 1:
The vaccine employs chimeric polypeptides constructed from segmented domains of FhbB proteins from different T. denticola strains. These modular constructs include specific functional domains (such as the Factor H binding domain) that can be independently optimized and assembled to create multi-epitope vaccines capable of inducing broad protective immunity
Solution Approach 2:
The recombinant chimeric FhbB proteins are designed to be universal across different T. denticola strains by incorporating conserved functional domains that are present in all strains. This multi-strain coverage allows a single vaccine formulation to provide broad protection against diverse bacterial variants
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 chimeric proteins effectively prevent and treat periodontal disease by inducing antibodies that target and kill T. denticola, preventing its binding to Factor H and maintaining a healthy immunological environment, thereby addressing the immune dysregulation caused by T. denticola.
Implementation Method 1
Administration of a chimeric protein comprising a plurality of mutant FhbB proteins to a subject elicits production of antibodies to the chimeras. The production of the antibodies prevents and/or treats PD through at least two distinct but synergistic mechanisms: 1) antibody-mediated complement dependent killing of T. denticola bacteria
Implementation Method 2
antibody-mediated complement dependent killing of T. denticola bacteria
Implementation Method 3
The mutations that are introduced result in forms of the FhbB proteins that no longer bind FH. Administration of a chimeric protein comprising a plurality of mutant FhbB proteins to a subject elicits production of antibodies to the chimeras
Data Source
AI summary
Provided herein are recombinant Factor H Binding Protein B (FhbB) chimeric proteins comprising several different mutant variants of the Treponema denticola Factor H binding protein B (FhbB). The mutant variants cannot bind Factor H. The chimeric proteins are used to vaccinate subjects against periodontal disease either systemically and/or by direct application of antibodies generated against the chimeric proteins to the oral cavity (e.g. the gums) of a patient to prevent and/or treat periodontal disease.