Engineering an efficient poly-epitope vaccine against Toxoplasma gondii infection: A computational vaccinology study
Introduction
Toxoplasmosis is a parasitic, zoonotic and prevalent disease which is caused by toxoplasma gondii(T. gondii) [1,2]. T. gondii is known as an obligatory intracellular protozoan belonging to the phylum of Apicomplexa [3]. It has been reported, T. gondii is able to infect a wide variety of warm-blooded creatures including humans, livestock, wild animals and birds [4]. In both human and livestock, toxoplasmosis is known as one of the most important health threats which can cause huge economic damages [5]. In general, life cycle of T. gondii includes asexual and a sexual parts, the asexual cycle can be appeared in most hosts, whereas sexual cycle is mostly observed in cats [6]. Also, this parasite has three replication forms in hosts including; tachyzoites, bradyzoites (tissue cyst) and sporozoites (oocysts) [7], in humans, T. gondii is usually transmitted using consumption of raw foods contaminated with viable tissue cysts [1]. Toxoplasmosis in immunocompetent patients, shows no symptoms, whereas this disease in immunocompromised patients shows intensive symptoms such as nerve problems, eye problems and even death [[8], [9], [10]]. Despite the importance of toxoplasmosis, there is only one approved chemical vaccine (TOXOVAC) to prevent and treat this disease in animals. The reports have shown, application of this vaccine, owing to its severe side effects and low efficacy has been limited [[11], [12], [13]]. Therefore, identification of an effective method to prevent toxoplasmosis is vital for researchers who are studying in this field. So far, different strategies including live attenuated vaccine, inactivated vaccine and subunit vaccine have been employed to prevent toxoplasmosis [14]. Although these strategies have been able to lead to some effective results, it seems prevention of toxoplasmosis needs a more effective strategy. Today, the epitope-based vaccines applying different epitopes instead of whole antigens are suggested to prevent viral and bacterial infections [15]. As matter of fact, these vaccines using stimulation of both humoral and cellular immunities can lead to protective immunity against infections [16]. Consequently, identification and extraction of effective epitopes which can stimulate the immune system, are known as a vital step in designing epitope-based vaccines. Bioinformatics is a fast, precise and affordable science which merges different fields including computer and biology to analyze biological data. Nowadays, many online servers and tools have been generated using the bioinformatics science which can isolate the best MHCI, MHCII and B cell epitopes of antigenic proteins [15]. The current project was designed to engineer a novel poly-epitope vaccine against T. gondii infection. To do so, 10 protective antigens of T. gondii including BiP, GRA1, GRA2, GRA5, MIC8, MIC13, P30, PI1, SOD and Rop2 were extracted from VIOLIN database. Then, the best MHCI, MHCII and B cell epitopes of protective antigens were isolated by the most accurate bioinformatics tools, the predicted epitopes along with heparin-binding hemagglutinin (HBHA) of Mycobacterium tuberculosis (as a molecular adjuvant) were used to engineer a poly-epitope vaccine.
Section snippets
Collection of protein sequences
In the current project, the amino acid sequences of the antigenic proteins were collected from the UniProt database (https://www.uniprot.org/). The accession numbers of BiP, GRA1, GRA2, GRA5, MIC8, MIC13, P30, PI1, SOD and Rop2 antigens were A0A0F7V8D8, P13403, P13404, Q07828, Q9BIM7, B0LUH4, Q27000, B9QKZ5, Q0QWJ4 and Q27007, respectively.
B cell epitope prediction
To predict B cell epitopes of the antigenic proteins, different accurate online tools including IEBD (https://www.iedb.org/), Bcepred (//crdd.osdd.net/raghava/bcepred),%20BepiPred
Epitope prediction
In the current study, the most reliable online tools were applied for isolation of B cell epitopes. According to the results, the peptides including “73 TPSYVAFTDDDRKIGE 88”, “23 YAAEGGDNQSSAVSD 37”, “28 GVVNQGPVDVPFSGKP 43”, “23 GVAGSTRDVGSGGDDS 38”, “179 AGTCTRTDEGYKCDCP 194”, “209 GGEIECPGGRSETSGE 224”, “250 LTENPWQGNASSDKGAT 266”, “189 LNCGVDGVTYDNHCLR 204”, “123 GRTGGSDGGGEPPQTP 138” and “81 MKPPMSGGGGEPTGR 95” were identified as the best B cell epitopes of BiP, GRA1, GRA2, GRA5, MIC8,
Discussion
Nowadays, vaccination is known as one the most efficient medical strategies which has been able to decrease mortality rate in human societies [17]. Despite the importance and success of the conventional vaccination methods such as inactive and attenuated vaccine in prevention of the different diseases, these methods encounter serious limitations [18]. Hence, it seems modern approaches should be considered as substitution of the conventional vaccination methods. Bioinformatics is a part of the
Conclusion
The aim of the current study was designing an efficient poly-epitope vaccine using computational vaccinology. In this case, for the first time, 10 antigenic proteins of T. gondii including BiP, GRA1, GRA2, GRA5, MIC8, MIC13, P30, PI1, Rop2 and SOD were simultaneously applied for prediction of the best B cell, MHCI and MHCII epitopes. Then, to trigger, innate, humoral and cellular immunities, a vaccine was designed which contained HBHA, MHCI, B cell and MHCII segments, respectively. To
Author statement
All aspects of the project were done by Ali Forouharmehr.
Availability of data and materials
All materials and methods and obtained data from present work were reported in the article.
Ethics approval and consent to participate
Not applicable.
Consent of publication
Not applicable.
Funding
Not applicable.
Declaration of competing interest
The authors declare that there is no conflict of interest.
Acknowledgement
The author would like to thank faculty of agriculture of Lorsetan University because providing calm environment to research. The present project was done without funding support.
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