Plasmodium RH Fragment Segmentation for Malaria Vaccine Design
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Solution Overview
Problem
Current methods fail to effectively dissect and target the specific binding domains of Plasmodium reticulocyte Binding Protein homologues (RH) involved in the invasion of erythrocytes by malaria parasites, limiting the development of effective preventive and therapeutic measures against malaria.
Innovation Solution
Isolation and use of specific Plasmodium RH fragments, such as those comprising amino acid sequences from SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, and SEQ ID NO: 8, to inhibit the binding and invasion of Plasmodium into erythrocytes, including the production of antibodies and pharmaceutical compositions that target these fragments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If the entire Plasmodium RH protein is used as a target, then the binding capability to erythrocytes is maintained, but the complexity of the target increases and specific binding domains cannot be easily identified or targeted
Solution Approach 1:
The patent applies segmentation by dividing the large Plasmodium RH protein (up to 300 kDa) into smaller functional domains. Specifically, the protein is divided into multiple regions (N-terminal region, central region, C-terminal region) and further into domains (DBLα, DBLβ, DBLγ, RH domain). This segmentation allows researchers to identify and target specific binding domains rather than the entire complex protein, resolving the contradiction between maintaining binding capability and reducing target complexity for precise identification.
2Ease of manufacture
If specific binding domains are dissected from the large RH protein, then the target complexity for intervention is reduced, but the ability to effectively inhibit binding may be compromised without complete understanding of all interaction regions
Solution Approach 1:
The patent applies the extraction principle by isolating and characterizing specific binding domains (DBLα, DBLβ, DBLγ, RH domain) from the complete RH protein. These extracted domains are then used as targets for developing preventive measures such as antibodies and vaccines. This approach reduces the complexity of the target while maintaining effectiveness, as the extracted domains contain the critical binding functionality needed to inhibit parasite-erythrocyte interaction.
Solution Approach 2:
The patent applies local quality by identifying that different domains of the RH protein have different functions. The DBL domains are involved in erythrocyte binding while the RH domain has distinct functionality. By targeting specific domains with appropriate interventions (such as domain-specific antibodies), the patent achieves effective binding inhibition without needing to address the entire protein, thus improving ease of manufacture while maintaining reliability.
3Adaptability or versatility
If multiple invasion pathways are considered, then the versatility of the solution increases, but the complexity of identifying and targeting all relevant receptors and ligands increases
Solution Approach 1:
The patent applies universality by developing a domain-based targeting approach that can be applied across multiple invasion pathways. The identified domains (DBLα, DBLβ, DBLγ, RH domain) are conserved across different Plasmodium species and are involved in erythrocyte binding for multiple invasion pathways. This universal domain structure allows a single targeting strategy to be effective against multiple pathways, increasing versatility without proportionally increasing system complexity.
Data Source
AI summary
The present invention provides isolated polynucleotides, polypeptides, antibodies and/or vaccines for the prevention and/or treatment of malaria caused by Plasmodium falciparum and/or Plasmodium vivax. In particular, the polypeptide fragments are derived from the binding domain of the reticulocyte binding proteins of Plasmodium falciparum and/or Plasmodium vivax. The present invention also provides recombinant vaccines and their use in the prevention and/or treatment of malaria.