Chlamydia Vaccine Antigens for Cross-Serovar T Cell Immunity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for Chlamydia trachomatis infections are inadequate due to high prevalence, asymptomatic cases, and the risk of reinfection, particularly in HIV-positive individuals, necessitating a more effective vaccine strategy.
Innovation Solution
Development of Chlamydia sp. antigens, including modified MOMP polypeptides and chimeric MOMP VD polypeptides, delivered via nucleic acids, which induce robust T cell responses and cross-serovar immunity by prioritizing conserved domains and minimizing B cell epitopes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If native MOMP polypeptide is used as vaccine antigen, then B cell epitopes are abundant and antibody responses are elicited, but T cell responses are insufficient for protective immunity
Solution Approach 1:
The patent extracts and removes the variable domains (VD1-VD4) from the native MOMP polypeptide, retaining only the conserved domains. This extraction eliminates B cell epitopes located in the variable domains while preserving the conserved domains that elicit T cell responses, thereby resolving the contradiction between abundant antibody responses and insufficient T cell responses.
Solution Approach 2:
The patent modifies the MOMP polypeptide by selectively removing only the variable domains while preserving the conserved domains. This local modification creates a truncated antigen with altered epitope distribution, enriching for T cell epitopes in conserved regions while eliminating B cell epitopes in variable regions, thus achieving the desired shift in immune response profile.
2Reliability
If variable domains of MOMP are included in vaccine antigen, then B cell epitopes are maximized for antibody production, but cross-serovar immunity is reduced due to sequence variability
Solution Approach 1:
The patent extracts and removes the variable domains (VD1-VD4) that exhibit sequence variability across serovars. By eliminating these variable regions from the vaccine antigen, the patent achieves cross-serovar immunity through the conserved domains alone, resolving the contradiction between maximizing B cell epitopes and achieving cross-serovar protection.
Solution Approach 2:
The patent changes the antigen composition parameter by truncating the MOMP polypeptide to exclude variable domains. This parameter change shifts the epitope profile from one dominated by serovar-specific B cell epitopes to one dominated by cross-serovar T cell epitopes located in conserved domains.
3Ease of manufacture
If full-length native MOMP is used as vaccine, then comprehensive epitope coverage is provided, but manufacturing complexity and purification difficulty increase
Solution Approach 1:
The patent extracts and removes the variable domains from the native MOMP polypeptide to create a truncated antigen. This extraction simplifies the antigen structure, reducing manufacturing complexity and purification difficulty while maintaining essential immunogenic properties through the conserved domains.
Solution Approach 2:
The patent employs a simplified truncated antigen structure that is easier and cheaper to manufacture than the full-length native MOMP. The truncated antigen requires less complex purification processes and can be produced more efficiently, aligning with the principle of using simpler, more economical antigen forms.
Data Source
AI summary
This invention relates to compositions (e.g., vaccine compositions) which can be used to immunise against Chlamydia infections. The compositions comprise Chlamydia sp. antigens and antigen combinations which can be used to immunise against Chlamydia sp., used in the form of nucleic acids (e.g., mRNAs) encoding antigenic proteins or in the form of recombinant protein antigens.