Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases
Robert Adamu Shey,
Stephen Mbigha Ghogomu,
Cabirou Mounchili Shintouo,
Francis Nongley Nkemngo,
Derrick Neba Nebangwa,
Kevin Esoh,
Ntang Emmaculate Yaah,
Muyanui Manka’aFri,
Joel Ebai Nguve,
Roland Akwelle Ngwese,
Ferdinand Ngale Njume,
Fru Asa Bertha,
Lawrence Ayong,
Rose Njemini,
Luc Vanhamme,
Jacob Souopgui
Affiliations
Robert Adamu Shey
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon
Stephen Mbigha Ghogomu
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon
Cabirou Mounchili Shintouo
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon
Francis Nongley Nkemngo
Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea 99999, Cameroon
Derrick Neba Nebangwa
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon
Kevin Esoh
Division of Human Genetics, Health Sciences Campus, Department of Pathology, University of Cape Town, Anzio Rd, Observatory, Cape Town 7925, South Africa
Ntang Emmaculate Yaah
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon
Muyanui Manka’aFri
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon
Joel Ebai Nguve
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon
Roland Akwelle Ngwese
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon
Ferdinand Ngale Njume
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon
Fru Asa Bertha
Department of Public Health and Hygiene, Faculty of Health Science, University of Buea, Buea 99999, Cameroon
Lawrence Ayong
Malaria Research Unit, Centre Pasteur Cameroon, Yaoundé Rue 2005, Cameroon
Rose Njemini
Frailty in Ageing Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium
Luc Vanhamme
Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM, Université Libre de Bruxelles, Gosselies Campus, 6040 Gosselies, Belgium
Jacob Souopgui
Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM, Université Libre de Bruxelles, Gosselies Campus, 6040 Gosselies, Belgium
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.
