Identification of antigenic linear peptides in the soil-transmitted helminth and Schistosoma mansoni proteome

Abstract

The scientific community identified non stool-based biomarkers as the way forward to support soil-transmitted helminth (STH; Ascaris lumbricoides, Trichuris trichiura and the hookworms Ancylostoma duodenale and Necator americanus) and schistosome (S. mansoni and S. haematobium) deworming programs. This support is needed in making the decision of whether or not to stop preventive chemotherapy intervention efforts and to ultimately transition towards a post-intervention surveillance phase. We applied a two-step micro-array approach to identify antigenic linear epitopes in the STH and S. mansoni proteomes. In a first experiment, we identified antigenic peptides by applying sera from 24 STH and/or S. mansoni infected Ethiopian children on a high-density peptide microarray containing 3.3 million peptides derived from the complete STH and S. mansoni proteomes. A second array experiment with 170,185 peptides that were recognized in the first array was designed to identify non-specific antibody reactivity by applying sera from 24 healthy individuals from Belgium (a non-endemic country). From this array testing cascade, several peptides were identified for STH but none of them appeared to be unique for one species. We therefore concluded that for STH, none of the peptides revealed to be sufficiently sensitive or species specific. For S. mansoni, some promising peptides were identified prompting future investigation. Based on these results, it is unlikely that linear epitopes would be highly useful in detecting species-specific antibody responses to STH in endemic communities. For S. mansoni, one particular peptide of the micro-exon gene 12 (MEG-12) protein deserves further research. In addition, this study emphasizes the need of well-characterized biobanks for biomarker discovery, particularly when the integration of multiple disease programs is envisioned.

Affordable artificial intelligence-based digital pathology for neglected tropical diseases: A proof-of-concept for the detection of soil-transmitted helminths and Schistosoma mansoni eggs in Kato-Katz stool thick smears

“…Today, the WHO already published TPPs for lymphatic filariasis [ 6 ], onchocerciasis [ 7 ], soil-transmitted helminthiasis [ 8 ], and schistosomiasis [ 9 ], while TPPs for other NTDs are in preparation. However, the pathway to translate new diagnostic biomarkers from initial discovery into an affordable laboratory or point-of-care diagnostic test for endemic programs remains long, expensive, and uncertain [ 10 , 11 ]. As a consequence of this, prioritising diagnostics based on new biomarkers for the WHO targets is extremely ambitious, and in the long run, may turn into an “appeal-to-future-discovery fallacy” [ 3 ].…”

Comparison of coproprevalence and seroprevalence to guide decision-making in national soil-transmitted helminthiasis control programs: Ethiopia as a case study

“…[ 30 ]. The call for species-specific and/or pan-helminth biomarkers stresses the need for well-characterized biobanks containing serum samples that are much better defined [ 48 ]. To date, FIND takes up a leading role in biobank services, with a network of integrated biobanks storing more than 400,000 samples to support the development of tools improving the diagnosis of infectious diseases in low- and middle-income countries ( https://www.finddx.org ).…”

“…Currently, there is no FIND biobank that includes characterization of samples regarding STH infections, and this might be an important step in streamlining the development of new STH diagnostics. As recently discussed by Vlaminck and colleagues, blood samples could be collected from different populations: longitudinal samples in endemic areas from subjects with changing infection status (strategy 1), samples from young children in areas endemic for only a single STH (strategy 2), samples from experimentally infected non-endemic individuals (strategy 3) or samples from experimentally infected animals using the original or a closely related parasite species (strategy 4) [ 48 ]. Sampling strategy 1 was recently applied by Dana and colleagues, indeed resulting in important insights into the potential of serodiagnostics in young children [ 32 ].…”

Antigen discovery by bioinformatics analysis and peptide microarray for the diagnosis of cystic echinococcosis

“…As recently reviewed [ 16 ], in the field of human parasitic infections, the microarray technology has been previously explored for the characterization of new diagnostic antigens especially for protozoan infections and, in particular in silico prediction of B-cell epitopes, has been mainly applied with positive results in the field of toxoplasmosis [ 52 , 53 ]. Concerning human helminth infections, the peptide microarray approach for antigen discovery with diagnostic scope has been used so far in a very limited number of studies targeting Schistosoma mansoni [ 54 ], Onchocerca volvulus [ 55 ], and, as said, Echinococcus spp. [ 14 ].…”