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

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dc.contributor.authorShey, Robert Adamu
dc.contributor.authorGhogomu, Stephen Mbigha
dc.contributor.authorShintouo, Cabirou Mounchili
dc.contributor.authorNkemngo, Francis Nongley
dc.contributor.authorNebangwa, Derrick Neba
dc.contributor.authorEsoh, Kevin
dc.contributor.authorYaah, Ntang Emmaculate
dc.contributor.authorManka’aFri, Muyanui
dc.contributor.authorNguve, Joel Ebai
dc.contributor.authorNgwese, Roland Akwelle
dc.contributor.authorNjume, Ferdinand Ngale
dc.contributor.authorBertha, Fru Asa
dc.contributor.authorAyong, Lawrence
dc.contributor.authorNjemini, Rose
dc.contributor.authorVanhamme, Luc
dc.contributor.authorSouopgui, Jacob
dc.date.accessioned2021-10-19T15:03:57Z
dc.date.available2021-10-19T15:03:57Z
dc.date.issued2021-01-21
dc.date.updated2021-02-26T14:53:19Z
dc.description.abstractOnchocerciasis 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.en_US
dc.identifierdoi: 10.3390/pathogens10020099
dc.identifier.apacitationShey, R. A., Ghogomu, S. M., Shintouo, C. M., Nkemngo, F. N., Nebangwa, D. N., Esoh, K., ... Souopgui, J. (2021). Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases. <i>Pathogens</i>, 10(2), http://hdl.handle.net/11427/35270en_ZA
dc.identifier.chicagocitationShey, Robert Adamu, Stephen Mbigha Ghogomu, Cabirou Mounchili Shintouo, Francis Nongley Nkemngo, Derrick Neba Nebangwa, Kevin Esoh, Ntang Emmaculate Yaah, et al "Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases." <i>Pathogens</i> 10, 2. (2021) http://hdl.handle.net/11427/35270en_ZA
dc.identifier.citationShey, R.A., Ghogomu, S.M., Shintouo, C.M., Nkemngo, F.N., Nebangwa, D.N., Esoh, K., Yaah, N.E. & et al. 2021. Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases. <i>Pathogens.</i> 10(2) http://hdl.handle.net/11427/35270en_ZA
dc.identifier.ris TY - Journal Article AU - Shey, Robert Adamu AU - Ghogomu, Stephen Mbigha AU - Shintouo, Cabirou Mounchili AU - Nkemngo, Francis Nongley AU - Nebangwa, Derrick Neba AU - Esoh, Kevin AU - Yaah, Ntang Emmaculate AU - Manka’aFri, Muyanui AU - Nguve, Joel Ebai AU - Ngwese, Roland Akwelle AU - Njume, Ferdinand Ngale AU - Bertha, Fru Asa AU - Ayong, Lawrence AU - Njemini, Rose AU - Vanhamme, Luc AU - Souopgui, Jacob AB - 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. DA - 2021-01-21 DB - OpenUCT DP - University of Cape Town IS - 2 J1 - Pathogens KW - Onchocerca volvulus KW - Ov-DKR-2 KW - chimeric antigen KW - IgG KW - vaccine development LK - https://open.uct.ac.za PY - 2021 T1 - Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases TI - Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases UR - http://hdl.handle.net/11427/35270 ER - en_ZA
dc.identifier.urihttps://doi.org/10.3390/pathogens10020099
dc.identifier.urihttp://hdl.handle.net/11427/35270
dc.identifier.vancouvercitationShey RA, Ghogomu SM, Shintouo CM, Nkemngo FN, Nebangwa DN, Esoh K, et al. Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases. Pathogens. 2021;10(2) http://hdl.handle.net/11427/35270.en_ZA
dc.language.isoenen_US
dc.publisher.departmentDepartment of Pathologyen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourcePathogensen_US
dc.source.journalissue2en_US
dc.source.journalvolume10en_US
dc.source.urihttps://www.mdpi.com/journal/pathogens
dc.subjectOnchocerca volvulus
dc.subjectOv-DKR-2
dc.subjectchimeric antigen
dc.subjectIgG
dc.subjectvaccine development
dc.titleComputational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseasesen_US
dc.typeJournal Articleen_US
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