Immunogenic Proteins Against Clostridium difficile Infection
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Solution Overview
Problem
Current therapies for Clostridium difficile infections are hindered by antibiotic resistance and physiological factors such as spore formation and the protective pseudomembrane, leading to a need for effective prevention and treatment methods.
Innovation Solution
Development of immunogenic proteins comprising domains from Clostridium difficile toxins TcdA and TcdB, along with Salmonella typhimurium flagellin, which induce a humoral and cell-mediated immune response, and are administered to prevent or treat infections by eliciting protective antibody responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibiotic treatment is used for Clostridium difficile infection, then the infection can be treated, but antibiotic resistance and physiological factors (spore formation, protective pseudomembrane) reduce effectiveness
Solution Approach 1:
The patent converts the harmful toxins TcdA and TcdB into beneficial immunogenic proteins by removing their transmembrane domains and toxic activities while retaining their receptor binding domains. This allows the previously harmful bacterial products to serve as protective vaccines that induce neutralizing antibodies against the toxins, transforming the harm into benefit.
Solution Approach 2:
The patent extracts and removes the transmembrane domains from the toxin proteins TcdA and TcdB, separating the harmful toxic activity from the useful receptor binding capability. By taking out the transmembrane domains, the proteins lose their ability to insert into cell membranes and cause toxicity, while retaining their ability to bind to receptors and serve as immunogens.
2Reliability
If full-length toxins TcdA and TcdB are used as immunogens, then strong immune response is elicited, but the toxins are toxic and cannot be administered
Solution Approach 1:
The patent extracts and removes the transmembrane domains from the full-length toxins TcdA and TcdB, separating the harmful toxic activity from the useful receptor binding capability. By taking out the transmembrane domains, the proteins lose their ability to insert into cell membranes and cause toxicity, while retaining their ability to bind to receptors and serve as immunogens.
Solution Approach 2:
The patent segments the full-length toxins into functional domains: the transmembrane domain (removed for safety) and the receptor binding domain (retained for immunogenicity). This segmentation allows the creation of safe immunogenic proteins that elicit protective immune responses without causing toxicity.
3Adaptability or versatility
If immunogenic proteins with transmembrane domains are used, then the proteins can bind to receptors, but the proteins become toxic when expressed in bacteria
Solution Approach 1:
The patent extracts and removes the transmembrane domains from the toxin proteins, separating the harmful toxic activity from the useful receptor binding capability. By taking out the transmembrane domains, the proteins lose their ability to insert into cell membranes and cause toxicity when expressed in bacteria, while retaining their ability to bind to receptors and serve as immunogens.
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 immunogenic proteins effectively induce potent anti-toxin neutralizing titers and provide full protection against Clostridium difficile infections, including hypervirulent strains, by enhancing the immune system's ability to respond to the toxins, thereby reducing disease severity and recurrence.
Implementation Method 1
which induce a humoral and cell-mediated immune response, and are administered to prevent or treat infections by eliciting protective antibody responses
Data Source
AI summary
Described are immunogenic proteins against Clostridium difficile. Also described are compositions comprising the immunogenic proteins. Further described are methods of preventing or treating a Clostridium difficile infection in a subject in need thereof.