Vaccinomics strategy to concoct a promising subunit vaccine for visceral leishmaniasis targeting sandfly and leishmania antigens

Autor: Vijay Kumar Prajapati, Rupal Ojha, Rajan Kumar Pandey
Rok vydání: 2020
Předmět:
Chemical Phenomena
medicine.medical_treatment
Molecular Conformation
Epitopes
T-Lymphocyte
Antigens
Protozoan
02 engineering and technology
Molecular Dynamics Simulation
Biology
Biochemistry
Epitope
Structure-Activity Relationship
03 medical and health sciences
Immunogenicity
Vaccine
Immune system
Antigen
Structural Biology
medicine
Animals
Leishmaniasis Vaccines
Molecular Biology
030304 developmental biology
Leishmania
0303 health sciences
Leishmaniasis
General Medicine
021001 nanoscience & nanotechnology
biology.organism_classification
medicine.disease
Virology
Sandfly
Molecular Docking Simulation
Toll-Like Receptor 4
Vaccinology
Visceral leishmaniasis
Host-Pathogen Interactions
Vaccines
Subunit
Epitopes
B-Lymphocyte
Leishmaniasis
Visceral
Psychodidae
0210 nano-technology
Adjuvant
T-Lymphocytes
Cytotoxic
Zdroj: International Journal of Biological Macromolecules. 156:548-557
ISSN: 0141-8130
DOI: 10.1016/j.ijbiomac.2020.04.097
Popis: 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 Ramachandran 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.
Databáze: OpenAIRE
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