Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases

Shey, Robert  Adamu; Ghogomu, Stephen  Mbigha; Shintouo, Cabirou  Mounchili; Nkemngo, Francis  Nongley; Nebangwa, Derrick  Neba; Esoh, Kevin; Yaah, Ntang  Emmaculate; Manka’aFri, Muyanui; Nguve, Joel  Ebai; Ngwese, Roland  Akwelle; Njume, Ferdinand  Ngale; Bertha, Fru  Asa; Ayong, Lawrence; Njemini, Rose; Vanhamme, Luc; Souopgui, Jacob

Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases

Journal Article

2021-01-21

Journal Title

Pathogens

Link to Journal

https://www.mdpi.com/journal/pathogens

Department

Department of Pathology

Faculty

Faculty of Health Sciences

License

http://creativecommons.org/licenses/by/4.0/

Abstract

Onchocerciasis is a skin and eye disease that exerts a heavy socio-economic burden, particularly in sub-Saharan Africa, a region which harbours greater than 96% of either infected or at-risk populations. The elimination plan for the disease is currently challenged by many factors including amongst others; the potential emergence of resistance to the main chemotherapeutic agent, ivermectin (IVM). Novel tools, including preventative and therapeutic vaccines, could provide additional impetus to the disease elimination tool portfolio. Several observations in both humans and animals have provided evidence for the development of both natural and artificial acquired immunity. In this study, immuno-informatics tools were applied to design a filarial-conserved multi-epitope subunit vaccine candidate, (designated Ov-DKR-2) consisting of B-and T-lymphocyte epitopes of eight immunogenic antigens previously assessed in pre-clinical studies. The high-percentage conservation of the selected proteins and epitopes predicted in related nematode parasitic species hints that the generated chimera may be instrumental for cross-protection. Bioinformatics analyses were employed for the prediction, refinement, and validation of the 3D structure of the Ov-DKR-2 chimera. In-silico immune simulation projected significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-γ, and IL-2 responses. Preliminary immunological analyses revealed that the multi-epitope vaccine candidate reacted with antibodies in sera from both onchocerciasis-infected individuals, endemic normals as well as loiasis-infected persons but not with the control sera from European individuals. These results support the premise for further characterisation of the engineered protein as a vaccine candidate for onchocerciasis.