Abstract
Dengue poses a global health threat, which will persist without therapeutic intervention. Immunity induced by exposure to one serotype does not confer long-term protection against secondary infection with other serotypes and is potentially capable of enhancing this infection. Although vaccination is believed to induce durable and protective responses against all the dengue virus (DENV) serotypes in order to reduce the burden posed by this virus, the development of a safe and efficacious vaccine remains a challenge. Immunoinformatics and computational vaccinology have been utilized in studies of infectious diseases to provide insight into the host–pathogen interactions thus justifying their use in vaccine development. Since vaccination is the best bet to reduce the burden posed by DENV, this study is aimed at developing a multi-epitope based vaccines for dengue control. Combined approaches of reverse vaccinology and immunoinformatics were utilized to design multi-epitope based vaccine from the sequence of DENV. Specifically, BCPreds and IEDB servers were used to predict the B-cell and T-cell epitopes, respectively. Molecular docking was carried out using Schrödinger, PATCHDOCK and FIREDOCK. Codon optimization and in silico cloning were done using JCAT and SnapGene respectively. Finally, the efficiency and stability of the designed vaccines were assessed by an in silico immune simulation and molecular dynamic simulation, respectively. The predicted epitopes were prioritized using in-house criteria. Four candidate vaccines (DV-1–4) were designed using suitable adjuvant and linkers in addition to the shortlisted epitopes. The binding interactions of these vaccines against the receptors TLR-2, TLR-4, MHC-1 and MHC-2 show that these candidate vaccines perfectly fit into the binding domains of the receptors. In addition, DV-1 has a better binding energies of − 60.07, − 63.40, − 69.89 kcal/mol against MHC-1, TLR-2, and TLR-4, with respect to the other vaccines. All the designed vaccines were highly antigenic, soluble, non-allergenic, non-toxic, flexible, and topologically assessable. The immune simulation analysis showed that DV-1 may elicit specific immune response against dengue virus. Moreover, codon optimization and in silico cloning validated the expressions of all the designed vaccines in E. coli. Finally, the molecular dynamic study shows that DV-1 is stable with minimum RMSF against TLR4. Immunoinformatics tools are now applied to screen genomes of interest for possible vaccine target. The designed vaccine candidates may be further experimentally investigated as potential vaccines capable of providing definitive preventive measure against dengue virus infection.
Highlights
Dengue poses a global health threat, which will persist without therapeutic intervention
12.5% of the world population are affected by a group of pathogens known to cause neglected tropical diseases (NTDs) (CDC, 2020)
Apart from condemning affected people to live with disability and stigma, these NTDs deprive children from attending school, threaten job security, increase the financial burden on countries due to medical cost and in turn negatively affecting the economy of developing countries[2,3,4]
Summary
Dengue poses a global health threat, which will persist without therapeutic intervention. 12.5% of the world population are affected by a group of pathogens known to cause neglected tropical diseases (NTDs) (CDC, 2020) This diverse group of tropical infections are common among the lowincome countries in developing regions of the world. There are several potential dengue vaccines at different stages of development in clinical trial with only one licensed for use Most of these vaccines are primarily developed from the envelope proteins prM and E, which are expected to elicit protective immune responses in h umans[13,14]. In May 2019, Dengvaxia was licensed and approved by the US Food and Drug Administration (FDA) in the United States in areas where dengue was prevalent This vaccine is available in 19 countries, and its use is limited to for a particular age range and cannot be administered in Flavivírus-naïve individual[18]. Due to the increased rate of hospitalization occurring in seronegative vaccinated children between the age of 9–11, Dengvaxia was predicted as vaccine failures rather than as vaccine enhanced dengue d isease[23]
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