Evaluation of Synthetic Peptides from Schistosoma mansoni ATP Diphosphohydrolase 1: In Silico Approaches for Characterization and Prospective Application in Diagnosis of Schistosomiasis

TL;DR

Researchers tested synthetic peptides from a Schistosoma mansoni enzyme to develop better diagnostic tools for schistosomiasis, a parasitic disease.

Contribution

The study introduces novel synthetic peptides from SmATPDase1 as potential diagnostic biomarkers for schistosomiasis.

Findings

Synthetic peptides from SmATPDase1 elicited strong antibody responses in mice.

Peptides showed high seropositivity in ELISA tests with AUC values over 0.9.

Monoclonal antibodies against the peptides recognized the full protein in diagnostic assays.

Abstract

Schistosomiasis is the infection caused by Schistosoma
mansoni and constitutes a worldwide public health
problem. The parasitological recommended method and serological methods
can be used for the detection of eggs and antibodies, respectively.
However, both have limitations, especially in low endemicity areas.
Thus, new approaches for the diagnosis of schistosomiasis are essential.
In this study, a six-amino acid peptide and derived sequences from
SmATPDase1 were synthesized for the evaluation of immunogenicity.
SmATPDase1 is included in a protein group in S. mansoni tegument; therefore, its peptides could be potential candidates
for diagnostic antigens. In the hypothetical SmATPDase1 three-dimensional
structure, peptides are located in a region exposed and accessible
to antibody binding. In addition, peptide amino acid sequences are
conserved in the most relevant Schistosoma species and have low identity with human NTPDases isoforms. Swiss
mice immunization resulted in significant anti-peptide polyclonal
antibodies production, which recognized a 63 kDa protein in tegument
and adult worm preparations. By immunofluorescence microscopy, polyclonal
antibodies also identified this enzyme in cercariae. Sera of infected
animals presented high seropositivity in ELISA-peptides, with an area
under curve (AUC) greater than 0.96 for all peptides. In mice with
low parasite burden, we observed a seropositivity AUC > 0.9. Reactivity
in the prepatent period exhibited AUC values greater than 0.94 for
all peptides. Anti-P1425 monoclonal antibodies were successfully produced,
and mAbs recognized the integral protein in ELISA and Western blots.
The data indicate that peptides from SmATPDase1 are potential biomarkers
for schistosomiasis, and anti-peptide antibodies are interesting tools
for the detection of the infection.

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