Signal Peptide Multi-Epitope Vaccine for Intracellular Pathogens
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Solution Overview
Problem
Current vaccines against intracellular pathogens like Mycobacterium tuberculosis, HIV, and malaria are ineffective and lack comprehensive immune responses, particularly in activating both CD4+ and CD8+ T cells, leading to inadequate protection against infections.
Innovation Solution
Development of peptide vaccines that incorporate signal peptide domains from target pathogens, recognized by multiple MHC class I and II alleles, to induce robust immune responses by activating both CD4+ and CD8+ T cells, using specific amino acid sequences that bind to over 50% of the population's MHC alleles, thereby preventing intracellular pathogen development.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If live attenuated pathogens are used as vaccines, then some level of immunity is achieved, but the effectiveness is variable (0-80%) and immunity wanes after 10-15 years
Solution Approach 1:
The patent extracts specific signal peptide sequences from pathogen proteins that are responsible for MHC binding and T cell activation, separating these protective epitopes from the entire live attenuated pathogen. This allows isolation of the most effective immunogenic components while eliminating the variability and waning issues associated with whole-pathogen vaccines.
Solution Approach 2:
The patent modifies the vaccine approach by changing from whole-pathogen to peptide-based vaccination, specifically selecting signal peptides with optimized MHC binding properties. The signal peptides are engineered to bind promiscuously to multiple MHC class I and II alleles, ensuring broad and sustained T cell activation without the limitations of live attenuated vaccines.
2Reliability
If vaccines target specific MHC alleles, then strong immune response is achieved in certain populations, but coverage is limited to less than 50% of the population
Solution Approach 1:
The patent designs signal peptide-based vaccines that simultaneously bind to multiple MHC class I and II alleles across different populations. The selected signal peptides have promiscuous binding properties, allowing a single vaccine formulation to elicit immune responses in over 50% of the population by covering diverse MHC allele types.
Solution Approach 2:
The patent segments the pathogen proteins into multiple signal peptide epitopes, each with different MHC binding specificities. By combining multiple signal peptides with complementary MHC allele coverage, the vaccine achieves both strong immune response in individuals and broad population coverage.
3Reliability
If traditional vaccines are used, then some protection is provided, but they fail to activate both CD4+ and CD8+ T cells comprehensively
Solution Approach 1:
The patent merges signal peptide sequences that can be processed and presented through both MHC class I and MHC class II pathways. This dual-pathway design ensures comprehensive activation of both CD8+ cytotoxic T cells (via MHC class I) and CD4+ helper T cells (via MHC class II), providing robust and multifaceted immune protection.
Data Source
AI summary
The invention provides peptide vaccines comprising the signal peptide domain of selected target antigens of intracellular pathogens. The peptide vaccines of the invention contain multiple class II and class I-restricted epitopes and are recognized and presented by the majority of the vaccinated human population. The invention provides in particular anti tuberculosis vaccines. The invention further provides compositions comprising the vaccines as well as their use to treat or prevent infection.