Schistosoma mansoni represents a significant etiological agent of schistosomiasis, a neglected tropical disease with a global distribution. Although the Kato-Katz technique is an effective diagnostic tool in areas with a high prevalence of the disease, it lacks sensitivity in regions with lower prevalence. The objective of this study was to identify and validate novel immunogenic peptide targets derived from the S. mansoni proteome. The initial set of 14,499 predicted sequences were obtained from the WormBase database, and it was filtered to 8,308 by removing proteins lacking start or stop codons, shorter than 100 amino acids, or with undetermined amino acids. The sequences were then cross-referenced for cross-reactivity and ranked based on B-cell immunogenicity, resulting in the selection of 442 peptides for synthesis and screening. Immunoblotting revealed 22 reactive peptides, with 15 exhibiting specificities for sera from individuals at the initial infection (T0) stage and five reactive to both T0 and post-treatment (30D) sera. Subsequently, 19 peptides were subjected to further validation through molecular weight assessment and synthesized for ELISA testing. The multi-peptide pool demonstrated a reactivity frequency of 54.5 % in infected individuals, which surpassed the reactivity frequencies observed for individual peptides. The six peptides exhibiting the highest reactivity were subsequently analyzed according to infection intensity. The multi-peptide pool exhibited the highest reactivity (65.2 %) in low-intensity cases. ROC curve analysis indicated that Peptide 15 demonstrated the highest sensitivity (78.79 %) and specificity (87.5 %), while the multi-peptide pool exhibited 67.65 % sensitivity and 81.82 % specificity. These findings highlight the potential of peptide-based diagnostics to enhance the detection and control of schistosomiasis.
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