Bacteriophage-Fused Peptides for Serodiagnosis of Human Strongyloidiasis

Abstract

BackgroundStrongyloidiasis, a human intestinal infection caused by the nematode Strongyloides stercoralis, is frequently underdiagnosed and although its high prevalence is still a neglected parasitic disease because conventional diagnostic tests based on parasitological examination (presence of Strongyloides larvae in stool) are not sufficiently sensitive due to the low parasitic load and to the irregular larval output. There is an urgent need to improve diagnostic assays, especially for immunocompromised patients with high parasitic load as consequence of self-infection cycle, which can disseminate throughout the body, resulting in a potentially fatal hyperinfection syndrome often accompanied by sepsis or meningitis.Methods/Principal FindingsWe have performed Phage Display technology to select peptides that mimic S. stercoralis antigens, capable of detecting a humoral response in patients with strongyloidiasis. The peptides reactivity was investigated by Phage-ELISA through different panels of serum samples. We have successfully selected five peptides with significant immunoreactivity to circulating IgG from patients' sera with strongyloidiasis. The phage displayed peptides C9 and C10 presented the highest diagnostic potential (AUC>0.87) with excellent sensitivity (>85%) and good specificity (>77.5%), suggesting that some S. stercoralis antigens trigger systemic immune response.Conclusions/SignificanceThese novel antigens are interesting serum biomarkers for routine strongyloidiasis screenings due to the easy production and simple assay using Phage-ELISA. Such markers may also present a promising application for therapeutic monitoring.

Theranostic applications of phage display to control leishmaniasis: selection of biomarkers for serodiagnostics, vaccination, and immunotherapy

“…Thus, it has been successfully applied to identify mimotopes used to diagnose malaria (22) (23) , toxoplasmosis (24) (25) , hepatitis A (26) , neurocysticercosis (27) , strongyloidiasis (28) , thyroid cancer (29) , Chagas' disease (30) , and bovine anaplasmosis (31) , and to develop vaccine candidates against cysticercosis (32) , herpes simplex virus infection (33) , cancer (34) , taeniasis (35) , hepatitis B (36) , trichinellosis (37) , Alzheimer's disease (38) , and bovine anaplasmosis (39) . Phage display technology has been also instrumental in the selection of therapeutic agents to treat various cancers such as glioblastoma, melanoma, leukemia, and prostate and thyroid cancers (40) (41) .…”

“…In another study, three peptides expressed in reactive phage clones and selected against serum from leprosy patients were successfully validated as tools for serological diagnosis of leprosy (44) . A similar approach has been applied to develop diagnostics for other animal and human diseases, such as neurocysticercosis (27) , strongyloidiasis (28) , and bovine anaplasmosis (39) . Phage particles carrying antigenic determinants may be directly used for therapy.…”

The Epidemiology of Human Strongyloidiasis

“…These assays show variable sensitivity and specificity, depending on the antigen used (crude extract or recombinant antigens) and population tested [27,30]. Currently, there is a need to improve the tools available for the diagnosis of this parasite, and for this, it will be very important to incorporate new technologies (i.e., LIPS or multiplex assays), as well as the search for new recombinant antigens (i.e., phage display technology) [29,31,32]. In order to be useful for the understanding of the epidemiology of strongyloidiasis and its clinical circumstances, there is a need for a better understanding of the accuracy and dynamics of antibody decay in response to curative antiparasitary regimens [27].…”

Subtractive phage display selection for screening and identification of peptide sequences with potential use in serodiagnosis of paracoccidioidomycosis caused by Paracoccidioides brasiliensis

“…) and strongyloidiasis (Feliciano et al . ). Using the monoclonal antibody anti‐gp75 of P. brasiliensis as a target, our group selected, by phage display, a peptide with potential application in PCM diagnosis (Caldini et al .…”