Abstract
Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality. The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito. In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response. This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins. Designed subunit vaccine was evaluated for its immunogenicity, allergenicity and physiochemical parameters. To enhance the stability of vaccine protein, disulfide engineering was performed in a region of high mobility. Codon adaptation and in silico cloning was also performed to ensure the higher expression of designed subunit vaccine in E. coli K12 expression system. Finally, molecular docking and simulation study was performed for the vaccine protein and TLR-4 receptor, to determine the binding free energy and complex stability. Moreover, the designed subunit vaccine was found to induce anti-salivary immunity which may have the ability to prevent the entry of Plasmodium sporozoites into the human host.
Highlights
Malaria still remains one of the most devastating and deadly infectious disease, which is characterized by the intermittent high fevers and it’s another form namely cerebral malaria, leads to the neurological complications such as brain injury and coma[1,2]
In order to design an immunogenic multi-epitope subunit vaccine, the sum of 33 A. stephensi salivary protein sequences was retrieved from the National Center for Biotechnology Information (NCBI) protein database
Malaria is severe infection characterized by the high fever with irregularity but may lead to brain injury and coma
Summary
Malaria still remains one of the most devastating and deadly infectious disease, which is characterized by the intermittent high fevers and it’s another form namely cerebral malaria, leads to the neurological complications such as brain injury and coma[1,2]. In this study, we applied a novel immunoinformatics approach to design multi-epitope based subunit vaccine that may prevent the disease by maintaining the host hemostasis by the inhibition of anticoagulant and anti-inflammatory proteins present in mosquito saliva. Vijay S. et al reported that salivary proteins might be utilized to develop novel antimalarial control strategies via innate immune protection against malaria[16] These proteins could likewise evoke a host IgG response in natural conditions[20,21]. This study represents a novel approach to develop malaria vaccine using salivary protein instead of parasitic protein, which could be helpful to prevent the Plasmodium infection to human host
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