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Prediction and validation of the structural features of Ov58GPCR, an immunogenic determinant of Onchocerca volvulus
Robert Adamu Shey1,2, Stephen Mbigha Ghogomu2, Ferdinand Ngale Njume1,2
1Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM Universite Libre de Bruxelles, Gosselies Campus, Gosselies, Hainaut, Belgium.
Abstract:
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.
Insights
New diagnostic tools for onchocerciasis (river blindness) are crucial. Researchers developed methods using the Ov58GPCR antigen and its peptides to detect active infections and monitor treatment success, aiding disease control efforts.
Area of Science:
- Parasitology
- Immunology
- Bioinformatics
Background:
- Onchocerciasis, a neglected tropical disease, causes significant morbidity, including blindness, and hinders socioeconomic development.
- Current control programs face challenges due to the lack of reliable tools for disease mapping and post-elimination surveillance.
- Accurate diagnostic and surveillance tools are essential for effective onchocerciasis control and elimination strategies.
Purpose of the Study:
- To develop novel diagnostic and surveillance tools for onchocerciasis using bioinformatics and immunological approaches.
- To investigate the potential of the Onchocerca volvulus G-protein coupled receptor (Ov58GPCR) and its extracellular domain (ECD) as diagnostic biomarkers.
- To assess the utility of Ov58GPCR-derived peptides and antibodies in distinguishing between infected, treated, and healthy individuals.
Main Methods:
- Bioinformatic analysis to identify conserved nematode antigens, specifically Ov58GPCR.
- Synthesis of peptides corresponding to the extracellular domain (ECD) of Ov58GPCR.
- Immunological assays including antibody production and peptide-based diagnostic tests.
- Analysis of Ov58GPCR transcription in different parasite stages.
- Measurement of IgG and IgE antibody responses to recombinant Ov58GPCR ECD in relation to ivermectin treatment.
Main Results:
- The Ov58GPCR antigen was identified as a conserved G-protein coupled receptor (GPCR) in nematodes.
- Synthetic peptides from Ov58GPCR's ECD were confirmed as immunogenic epitopes in infected individuals.
- Peptide cocktails demonstrated ability to differentiate between actively infected, treated, and healthy individuals.
- Polyclonal antibodies recognized the native Ov58GPCR antigen in O. volvulus extracts.
- Ov58GPCR is expressed in both larval and adult stages of the parasite.
- Ivermectin treatment led to a decline in IgG and IgE responses against the recombinant Ov58GPCR ECD.
Conclusions:
- The extracellular domain and synthetic peptides of Ov58GPCR show promise as diagnostic markers for onchocerciasis.
- Immune responses targeting Ov58GPCR can be used to assess treatment efficacy and for disease surveillance.
- These findings contribute to the development of much-needed tools for onchocerciasis control and potential elimination.
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