TY - JOUR
T1 - Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate against Onchocerciasis and Related Filarial Diseases
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
PY - 2021/2
Y1 - 2021/2
N2 - : 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.
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.
KW - IgG
KW - Onchocerca volvulus
KW - Ov-DKR-2
KW - chimeric antigen
KW - vaccine development
UR - http://www.scopus.com/inward/record.url?scp=85099742516&partnerID=8YFLogxK
U2 - 10.3390/pathogens10020099
DO - 10.3390/pathogens10020099
M3 - Article
C2 - 33494344
VL - 10
SP - 1
EP - 32
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 2
M1 - 99
ER -