In Silico Design and Validation of OvMANE1, a Chimeric Antigen for Human Onchocerciasis Diagnosis

The public health goal of onchocerciasis in Africa has advanced from control to elimination. In this light, accurate diagnosis is necessary to determine treatment endpoints and confirm elimination, as well as to conduct surveillance for the identification of any possible recrudescence of the disease. Currently, the monitoring of onchocerciasis elimination relies on the Ov-16 test. However, this test is unable to discriminate between past and active infections. Furthermore, about 15-25% of infected persons are reported to be negative for the Ov-16 test, giving a misleading sense of security to false-negative individuals who might continue to serve as reservoirs for infections. Therefore, we opted to design and validate a more sensitive and specific chimeric antigen (OvMANE1) for onchocerciasis diagnosis, using previously reported immunodominant peptides of O. volvulus, the parasite responsible for the disease. In silico analysis of OvMANE1 predicted it to be more antigenic than its individual peptides. We observed that OvMANE1 reacts specifically and differentially with sera from O. volvulus infected and non-infected individuals, as well as with sera from communities of different levels of endemicity. Moreover, we found that total IgG, unlike IgG4 subclass, positively responded to OvMANE1, strongly suggesting its complementarity to the Ov-16 diagnostic tool, which detects Ov-16 IgG4 antibodies. Overall, OvMANE1 exhibited the potential to be utilized in the development of specific diagnostic tools-based on both antibody capture and antigen capture reactions-which are indispensable to monitor the progress of onchocerciasis elimination programs.