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

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.

Co-Administration of Adjuvanted Recombinant Ov-103 and Ov-RAL-2 Vaccines Confer Protection against Natural Challenge in A Bovine Onchocerca ochengi Infection Model of Human Onchocerciasis

“…It is notable that there is a partial overlap between the sequence and position of epitope 3 of Ov-103 discovered here and that of a previous study where peptide arrays were performed using sera from patently O. volvulus infected humans [56]. Furthermore, both epitope 2 and 4 of Ov-103 identified in this study have also been identified as both human B-cell and helper T-cell epitope candidates through computational analysis, again suggesting a commonality between bovine and human responses, as well as a potential expansion of their role and importance to stimulation of adaptive T-cell responses [57]. Due to the small sample size, it was not possible to draw any conclusions on the importance of these epitope-specific responses for parasite killing.…”

Advancing a Human Onchocerciasis Vaccine From Antigen Discovery to Efficacy Studies Against Natural Infection of Cattle With Onchocerca ochengi

“…A preliminary immunological test with this multi-epitope vaccine candidate revealed its strong reaction to antibodies in sera from putatively immune or infected individuals living in O. volvulus -endemic areas as well as from loiasis individuals, but not with the normal control sera from European individuals. These results support its further evaluation as a vaccine candidate for onchocerciasis ( Shey et al., 2021 ). Immuno-informatics tools and high-density peptide array were used to screen the immunodominant epitopes from the same 8 promising vaccine candidates as mentioned above using sera from onchocerciasis patients and healthy controls.…”

A Systematic Immuno-Informatic Approach to Design a Multiepitope-Based Vaccine Against Emerging Multiple Drug Resistant Serratia marcescens

“…The higher the score, the higher the chance of inducing IFN-g (70). Although the IFN epitope server has limitations regarding the number of residues that can be used for prediction (71), it is a common online prediction server used for vaccine design (70,(72)(73)(74). Therefore, the epitopes with positive results for the IFN-g response were selected for further prediction.…”