Abstract
Dengue Fever (DF) has emerged as a significant public health problem of international concern with its high prevalence in the tropic and subtropical regions. Dengue Virus (DENV), which is the cause of DF, consists of four serotypes of antigenically distinct viruses. The immense variation and limited identity similarity at the amino acid level lead to a problematic challenge in the development of an efficacious vaccine. Fortunately, the extensively available immunological data, the advance in antigenic peptide prediction, and the incorporation of molecular docking and dynamics simulation in immunoinformatics have directed the vaccine development towards the rational design of the epitope-based vaccine. Here, we point out the current state of dengue epidemiology and the recent development in vaccine development. Subsequently, we provide a systematic review of our validated method and tools for B- and T-cell epitope prediction as well as the use of molecular docking and dynamics in evaluating epitope affinity and stability in the discovery of a new tetravalent dengue vaccine through computational epitope-based vaccine design.
Highlights
Vector-borne diseases infect over one billion people and are responsible for more than one million deaths annually [1]
The TDV vaccine (DENVax), another live attenuated tetravalent dengue vaccine which currently undertaking Phase III trials, is a safe and effective vaccine which comprise of attenuated Dengue Virus (DENV)-2 PDK-53 as the backbone as well as chimeras in which the DENV-2 prM and E were replaced by other serotypes (DENV-2/DENV-1, DENV-2/DENV-3, and DENV-2/DENV-4 chimeras) [70, 71]
The E protein is chosen as a target in epitope-based vaccine design because it is responsible for cell recognition, viral entry, and host cell immune system stimulation [40]
Summary
Vector-borne diseases infect over one billion people and are responsible for more than one million deaths annually [1]. The DHF patient may suddenly deteriorate after a few days of fever, followed by signs of circulatory failure, and may rapidly go into a critical state of shock This state, namely shock syndrome, is a fatal complication of dengue infection and is correlated with high mortality [13]. The complexity of DF, because of four related but antigenically distinct viruses, establishes a challenging condition to understand its ecology and immunology as well as to develop an efficacious vaccine against it [16, 22, 23] Some problems, such as the design of tetravalent vaccines and the absence of appropriate animal and human infections models, remain the primary obstacles for developing the productive yet efficient dengue vaccine [24]. We disclose our method in the discovery of a new tetravalent dengue vaccine through computational epitopebased vaccine design as a part of the modern DENV vaccine development [28 - 31]
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