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.
Highlights
Onchocerciasis, called river blindness, remains one of the greatest debilitating and stigmatizing yet neglected tropical diseases
This study focused on the computational design and preliminary in-vitro characterisation of a novel multi-epitope chimeric vaccine candidate against onchocerciasis using epitopes predicted from eight proteins previously tested in preclinical development. [75,79,80]
Ov-DKR-2, the multi-epitope peptide generated in this study showed antigenic scores higher than those of Ov-RAL-2 and Ov-103 both on the Vaxijen v2.0 and ANTIGENpro servers
Summary
Onchocerciasis, called river blindness, remains one of the greatest debilitating and stigmatizing yet neglected tropical diseases. The infective larval stages of the parasite are transmitted through the repeated bites of infective black flies of the genus Simulium. These later give rise to adult worms that dwell in subcutaneous tissues in the human hosts where they can survive for up to 15 years (even under drug pressure), with adult female worms hatching approximately. Though infections were previously associated mainly with skin and eye lesions, recent records show a trend towards increased mortality. Results from data collected over a 27-year period reported a 5.9% mortality risk attributable to onchocerciasis with greater excess mortality associated with a microfilarial load in younger hosts [3]. With approximately 20.9 million people currently infected, including 14.6 million people with
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