Prediction and validation of the structural features of Ov58GPCR, an immunogenic determinant of Onchocerca volvulus
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
... , 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. and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. ITS: 68 skin snip-negative persons from an onchocerciasis near-elimination (previously hyperendemic) setting. These persons were selected from 3 onchocerciasis-near elimination communities (two with microfilaridermia prevalence values of 0.0% and the 3rd with a prevalence of 10.0%). These persons were selected based on their microfilaria-negative status irrespective of ivermectin treatment status. LLS: 50 persons actively infected with Loa loa based on microfilariae data; the persons in this group were not parasitologically tested for onchocerciasis. ECS: 3 persons from onchocerciasis non-endemic settings; Apart from the serum samples from the Loa loa infected subjects, all the other samples used for this work were collected purposely for this study.