Computational Development of Transmission-Blocking Vaccine Candidates Based on Fused Antigens of Pre- and Post-fertilization Gametocytes Against Plasmodium falciparum DOI Creative Commons
Matthew A. Adeleke

Bioinformatics and Biology Insights, Journal Year: 2025, Volume and Issue: 19

Published: Jan. 1, 2025

Plasmodium falciparum is the most fatal species of malaria parasites in humans. Attempts at developing vaccines against have not been very successful even after approval RTS, S/AS01 vaccine. There a continuous need for more effective including sexual-stage antigens that could block transmission between mosquitoes and Low immunogenicity, expression, stability are some challenges transmission-blocking vaccine (TBV). This study was designed to computationally identify TBV candidates based on fused by combining highly antigenic peptides from prefertilization (Pfs230, Pfs48/45) postfertilization (Pfs25, Pfs28) gametocytes. The were selected their antigenicity, nonallergenicity, lack similarity with human proteome. Two (FAVCs) constructed using Flagellin Salmonella enterica (FAVC-FSE) Cholera toxin B (FAVC-CTB) as adjuvants. constructs evaluated physicochemical properties, structural stability, potential elicit cross-protection across multiple species. results yielded peptides, antigenicity scores 0.7589 1.1821. analysis FAVC-FSE FAVC-CTB showed Z-score -6.70 -4.79, Ramachandran plot 96.94% 94.86% overall quality 94.20% 89.85%, respectively. FAVCs contained CD8+, CD4+, linear B-cell epitopes 1.2089 2.8623, 0.5663 2.4132, 1.5196 2.2212, Each FAVC generated 6 conformational B-cells. High population coverage values recorded FAVCs. ability trigger immune response through an silico stimulation. low-binding interaction energy resulted molecular docking dynamics simulations strong affinity Toll-like receptor 5 (TLR5). indicate candidate promising interrupt P provides baseline experimental validation.

Language: Английский

Computational Development of Transmission-Blocking Vaccine Candidates Based on Fused Antigens of Pre- and Post-fertilization Gametocytes Against Plasmodium falciparum DOI Creative Commons
Matthew A. Adeleke

Bioinformatics and Biology Insights, Journal Year: 2025, Volume and Issue: 19

Published: Jan. 1, 2025

Plasmodium falciparum is the most fatal species of malaria parasites in humans. Attempts at developing vaccines against have not been very successful even after approval RTS, S/AS01 vaccine. There a continuous need for more effective including sexual-stage antigens that could block transmission between mosquitoes and Low immunogenicity, expression, stability are some challenges transmission-blocking vaccine (TBV). This study was designed to computationally identify TBV candidates based on fused by combining highly antigenic peptides from prefertilization (Pfs230, Pfs48/45) postfertilization (Pfs25, Pfs28) gametocytes. The were selected their antigenicity, nonallergenicity, lack similarity with human proteome. Two (FAVCs) constructed using Flagellin Salmonella enterica (FAVC-FSE) Cholera toxin B (FAVC-CTB) as adjuvants. constructs evaluated physicochemical properties, structural stability, potential elicit cross-protection across multiple species. results yielded peptides, antigenicity scores 0.7589 1.1821. analysis FAVC-FSE FAVC-CTB showed Z-score -6.70 -4.79, Ramachandran plot 96.94% 94.86% overall quality 94.20% 89.85%, respectively. FAVCs contained CD8+, CD4+, linear B-cell epitopes 1.2089 2.8623, 0.5663 2.4132, 1.5196 2.2212, Each FAVC generated 6 conformational B-cells. High population coverage values recorded FAVCs. ability trigger immune response through an silico stimulation. low-binding interaction energy resulted molecular docking dynamics simulations strong affinity Toll-like receptor 5 (TLR5). indicate candidate promising interrupt P provides baseline experimental validation.

Language: Английский

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