Computational Design of Ancestral and Consensus Asian Dengue Envelope Protein for Vaccine Candidate

Dengue is a mosquito-borne viral disease of which incidence has rapidly increased in the last few years. Despite the recent development of a licensed dengue vaccine, safer and more efficacious dengue vaccine still needs to be developed. Dengue virus has four antigenically and genetically distinct serotypes. Ancestral sequence reconstruction (ASR) and consensus sequence (CS) might be able to overcome antigenic distinction between those four serotypes. Envelope (E) protein is responsible for a wide range of dengue virus biological activities. Domain III of the E protein (EDIII) plays a role in receptor binding for viral entry and inducing protective immunity against the dengue virus. We utilised bioinformatics software to computationally design ancestral and consensus sequences of Asian dengue E protein. E protein sequences of 987 DENV strains and 5 outgroups were retrieved from GenBank. We constructed ancestral and consensus sequences for each serotype. For ASR, ancestral sequences were gradually designed to construct ancestral sequence for all serotypes using MEGA X. For CS, all four consensus sequences were directly used to construct consensus sequence for all serotypes using UGENE 1.32. Phylogenetic tree consisting existing dengue sequences as well as ancestral and consensus sequences were visualised using FigTree 1.4.4. All ancestral and consensus sequences were analysed for conserved motifs, especially in domain III region. ASR sequences were closer to the centre of phylogenetic tree branches while consensus sequences were located among natural isolates. Further CD4 T cell immunogenicity prediction on domain III (EDIII) showed that both ASR and consensus EDIII have the two-highest combined immunogenicity scores. These sequences are potential for further in vitro and in vivo studies as dengue vaccine candidate.   Keywords: ancestral sequence, consensus, dengue, envelope protein, vaccine