In silico prediction of CD8+ and CD4+ T cell epitopes in Leishmania major proteome: Using immunoinformatics

An obligatory intracellular protozoan parasite called Leishmania causes cutaneous, mucocutaneous, and visceral illnesses. Almost 90 nations in Africa, Asia, the Middle East, South and Central America are affected by leishmaniasis, a tropical disease that affects the world's poorest people [1,2]. Cutaneous leishmaniasis (CL), which is endemic to more than 100 countries, is one of the neglected tropical diseases brought on by several Leishmania species. In the Americas, the Middle East, the Mediterranean basin, and Central Asia, cutaneous leishmaniasis (CL) cases range from 700,000 to 1.2 million every year [ [1,3]. The present chemotherapies are expensive, have numerous adverse effects, are poorly tolerated, and exhibit drug resistance [4]. Thus, better therapy options other than medication discovery must be developed immediately. Many investigations have been conducted in this area, and a small number of vaccine formulations, such as live, killed, or attenuated parasites, DNA, or proteins, have also been created and evaluated in animal models [5]. Yet, the success rate is poor; hence it is urgently necessary to create novel ways for new vaccine candidates. In this situation, Immunoinformatics technique for epitope prediction and computation-based antigen prediction were used. Vaccinomics is the integration of immunology and bioinformatics for the creation of vaccines [6]. Prior researches were done to find potential vaccine candidates utilizing pathogen genomes. These techniques have already been used to find vaccines against a number of illnesses, including influenza, leishmania, dengue and malaria [4,[7], [8], [9]].

According to literature it is crucial to predict CD4+ and CD8+ T cell epitopes for the vaccine development process since an efficient vaccination will activate immune system and generated protective response [10,11]. These responses has been linked to the prevention of disease, activation of macrophages, and removal of parasites from the host [12,13]. Dendritic cells (DCs), which are specialized antigen-presentation cells (APCs), can prime naive T cells to fight Leishmania species by presenting antigenic peptides bound to MHCs (Major Histocompatibility Proteins), together with co-stimulating and secreting cytokines, as well as increases T cell response against parasite [11,14]. Leishmania mexicana and Leishmania amazonensis could fail to activate DCs, which would prevent a productive T cell response [15,16]. L. major, however, aids in the recruitment of DC, demonstrating the effect on the protective immune response [17]. Each mature DC is thought to express 105 MHC Class I (MHC I) molecules and 106-107 MHC Class II (MHC II) molecules [18]. Whereas 15-mer-peptides attached to MHC II activate CD4+ T cells and 9-mer-peptides bound to MHC I proteins specifically engage MHC I proteins to activate CD8+ T cells. Since experimental techniques are challenging and time-consuming, reverse vaccinology has reduced the enormous number of molecules that need to be examined and increased the chance of finding better candidates [19]. Reverse vaccinology technique uses genomic/proteomic sequences and predicts probable vaccine candidates using in silico methods [20]. Similarly, in order to forecast T- and B-cell immune epitopes for the production of epitope vaccines and analysis of protective immunity, numerous immunoinformatics methods and tools have been created [21].

Moreover, a large number of pathogen proteomes and genomes are currently accessible in open data repositories, allowing for evaluation of their potential antigen variety and diversity. Hence, the search for new antigens to promote vaccine development may be aided by sequence- and structure-based approaches that examine the binding affinity of peptides to class I and class II molecules along with other parameters [22]. The proteome of Leishmania spp. was searched for various epitopes by using sequence-based approaches by John et al. [20]. Recent research by Agallou et al. uses four well-known Leishmania infantum proteins to create a multi-epitope peptide vaccination against leishmaniasis [23].

In this context, we expected that a combination of contemporary sequencing and protein structure algorithms would aid the search for putative immunogenic epitopes with high affinity for both human MHC class I and MHC class II throughout the entire predicted proteome from L. major. Thus, the purpose of this research was to combine reliable in silico methods in the hunt for potentially immunogenic T cell epitopes, based on the proteome of L. major, in order to facilitate the production of an anti-Leishmania vaccine.

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