Strongyloides stercoralis proteome: A reverse approach to the identification of potential immunogenic candidates

Highlights

• Novel antigenic peptides were identified from the entire proteome of S. stercoralis.

• The bioinformatic tools led to the identification of 34 immunogenic candidate.

• The mayor immunogenic candidates were secreted proteins.

• The immunogenic candidate had high content of basic amino acids.

• The immunogenic candidate presented a good binding with T and B cell.

Abstract

Strongyloides stercoralis is a parasite widely distributed in the tropical and subtropical areas in the world. Its treatment and diagnosis have a limitation as many other parasitic diseases. Nowadays, there is a great interest in designing an efficient epitope for vaccines or diagnostic. In this study, a bioinformatics-based screening approach has been incorporated in order to explore potential immunogens in the S. stercoralis proteome. Bioinformatic tools were used to predict diagnostic and vaccinology approaches. 12.851 cell immunology proteins from Uniprot were analyzed. Thirty-four immunogenic candidates were identified, they had higher antigenic activity, less than 2 α-helices, non-allergen activity and they do not have homology with host proteins, all of them have ortholog protein with Strongyloides ratti. Some of them presented a good binding with immunological cell (T and B cell). These proteins could be a good alternative as a candidate for the design of the novel vaccines or diagnostic tests of strongyloides stercoralis.

Introduction

Strongyloidiasis is an infection by Strongyloides stercoralis, an earthworm that is found in tropical and subtropical areas. Human strongyloidiasis is caused by two species of the parasitic nematode. Strongyloides, S. stercoralis being the most frequent pathogen in humans; S. Fuelleborni, found sporadically in Africa and Papua New Guinea, and S. stercoralis are affecting around 370 million people worldwide, particularly in remote rural areas [1]. It is a neglected tropical disease that can lead to severe symptoms and even death in immunosuppressed people [2].

The parasite has a complex life cycle due to the possibility of a direct and indirect development or to produce internally and externally, parasitological techniques are the common tool for the diagnosis of strongyloidiasis; the coprological testing is the normal methodology, however, the sensitivity of traditional parasitological tests is low [[3], [4], [5], [6]]. With the purpose of improving the sensitivity of the diagnostic, another alternative technique has been tested, for example, molecular methods have proved to be highly sensitive and specific for detection of parasitic agents in fecal matter; however, there are discrepancies in the reported accuracy of PCR [7]. Other tests are serological and some of them are commercially available [1]. Nevertheless, for these tests, possible cross-reactions with other parasites have been proven and crude larval antigen require some special conditions and, for that reason, the process is laborious, slow and expensive [8]. Nonetheless, purified recombinant antigens or using synthetic peptides as antigens for immunodiagnostic increase the accuracy [9,10]. In the case of detection of S. stercoralis, the incorporation of other recombinants could increase the accuracy of this method. Some authors have identified proteins from excretory/secretory (E/S) products with potential as a possible immunogen for the production of antibodies in order to detect this parasite, for example [11]; describe fatty acid binding (FAB) and fatty acid and retinol-binding (FAR) as possible new immunogen that could be considered as an alternative diagnostic tool in ELISA.

Reverse vaccinology is a methodology that uses bioinformatic tools. Studies have shown many advantages: to reduce time, to refine the number of proteins to be studied facilitating the selection process, to decrease the number of validation experiments and the possibility to synthesize peptides for immunodiagnosis leading to the development of several high sensitivity and specificity tests in recent years. For this field, different sources have been used: the genomic, proteomic, and transcriptomic datasets of pathogens [12,13,14,15]. Considering that secreted/excreted proteins could be a good target in the detection of parasites or as possible immunological compounds. Bioinformatics tools become a fast and inexpensive alternative to identify these possible immunoreactive proteins of S. stercoralis. Bearing this in mind, the selection of the target molecules was based on the analysis of their, specificity, the duration of the immune response and their ability to create immunological memory.

A pipeline of algorithms was utilized for the prediction of novel antigenic peptides from the entire proteome of S. stercoralis. From the set of 12.858 proteins, 34 proteins were predicted to be the top candidate for the design of the novel vaccines or diagnostic tests.