Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 156, Issue -, Pages 548-557Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2020.04.097
Keywords
Adjuvant; Antigens; Leishmaniasis; Sandfly; Salivary protein; Vaccine
Funding
- UGC
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Visceral leishmaniasis (VL) has been declared as one of the most severely neglected tropical diseases by the World Health Organization report 2017. Cumulative incidences of treatment failure and drug resistance, demanding a potential treatment and preventive strategy for VL. In this study, we have devised a multi-epitope vaccine by targeting sandfly saliva and parasite-derived membrane and secretory antigens. We have predicted the immunogenic B-cell, HTL, and CTL epitopes from all the selected protein sequences. The epitopes were then linked to the spacer sequences for providing stability and flexibility, and the construct was linked with a synthetic TLR-4 agonist namely RS09 as an adjuvant. The 3D structure of vaccine was modelled, refined and validated by generating a Rarnachandran plot. Later, molecular docking was performed between the TLR-4 receptor and vaccine. The obtained docked complex was then checked for their stability by performing MD simulation. The immune dynamics simulation was done to check the probable immune response generated when the host will be exposed to the vaccine candidate. This novel vaccine strategy will provide functional and mechanistic evidence on parasite and vector-derived epitopes that could activate B- and T-cells and potentially elicit a long-lasting memory cell response. (C) 2020 Elsevier B.V. All rights reserved.
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