Journal Article

Prediction and validation of the structural features of Ov58GPCR, an immunogenic determinant of Onchocerca volvulus

Kamgno, Joseph, Vanhamme, Luc, Munyampundu, Jean-Pierre, Mutesa, Leon, Gainkam, Lea Olive Tchouate, Souopgui, Jacob, Shey, Robert Adamu, Ghogomu, Stephen Mbigha, Humblet, Perrine, Lelubre, Christophe, Njume, Ferdinand Ngale, Robert, Annie, Poelvoorde, Philippe

2018

Overview

Onchocerciasis is a severely debilitating yet neglected tropical disease (NTD) that creates social stigma, generates and perpetuates poverty, and leads ultimately in some cases to irreversible unilateral or bilateral blindness if untreated. Consequently, the disease is a major impediment to socioeconomic development. Many control programs have been launched for the disease with moderate successes achieved. This mitigated hit is partially due to the lingering need for reliable, non-invasive and easily applicable tools for mapping endemic regions and post-elimination surveillance. In this work, bioinformatics analyses combined with immunological assays were applied in a bid to develop potential tools for diagnosis and assessing the success of drug treatment programs. We report that (i) the O. volvulus antigen, Ov58GPCR is a G-protein coupled receptor (GPCR) conserved in related nematodes, (ii) synthetic peptides predicted to be in the extracellular domain (ECD) of Ov58GPCR are indeed immunogenic epitopes in actively-infected individuals, (iii) synthetic peptide cocktails discriminate between actively-infected individuals, treated individuals and healthy African controls, (iv) polyclonal antibodies against one of the peptides or against the bacterially-expressed ECD reacted specifically with the native antigen of O. volvulus total and surface extracts, (v) Ov58GPCR is transcribed in both larvae and adult parasite stages, (vi) IgG and IgE responses to the recombinant ECD decline with ivermectin treatment. All these findings suggest that the extracellular domain and synthetic peptides of Ov58GPCR, as well as the specific immune response generated could be harnessed in the context of disease diagnosis and surveillance.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / African river blindness nematode / Analysis / Animals / Antibodies / Antigens / Antigens, Helminth - metabolism / Antiparasitic Agents - therapeutic use / Bioinformatics / Biology and Life Sciences / Biotechnology / Blindness / Care and treatment / Chemotherapy / College campuses / Computational Biology / Control programs / Cross-Sectional Studies / Diagnosis / Disease / Disease control / Endemic Diseases / Enzymes / Epidemiological Monitoring / Epidemiology / Escherichia coli / Female / G protein-coupled receptors / Health sciences / Humans / Immune response / Immune system / Immunity, Humoral / Immunogenicity / Immunoglobulin E / Immunoglobulin E - metabolism / Immunoglobulin G / Immunoglobulin G - metabolism / Immunology / Infections / Ivermectin / Ivermectin - therapeutic use / Laboratories / Larvae / Male / Medicine / Medicine and Health Sciences / Molecular biology / Mortality / Neglected Diseases - diagnosis / Neglected Diseases - drug therapy / Neglected Diseases - epidemiology / Nematodes / Onchocerca volvulus - growth & development / Onchocerca volvulus - immunology / Onchocerciasis / Onchocerciasis - diagnosis / Onchocerciasis - drug therapy / Onchocerciasis - epidemiology / Parasites / Parasitology / Peptides / Polyclonal antibodies / Poverty / Predictions / Protein Domains / Proteins / Recombinant Proteins - metabolism / Research and Analysis Methods / Surveillance / Synthetic peptides / Treatment outcome / Tropical diseases / Tuberculosis / Young Adult