Dengue fever reported endemic in tropical and sub-tropical country. Dengue fever caused by dengue virus, has Envelope protein that often used for vaccine development to prevent the virus infection. Vaccine development to prevent four serotype dengue virus infection still unavailable. This study aims to design polytope from four conserved epitopes of dengue virus envelope glycoprotein to prevent infection of heterotypic dengue virus and predict its antigenic challenge by molecular docking. We investigate molecular modeling of polytope, immunoinformatics analysis of polytope, protein structure of antibodies, molecular docking and protein-protein docking assessment. The polytope categorized as a stabil protein with index 29.72, has molecular weight 6,139 kDa, has three exposed antigenic determinants region and has estimated half-life is: 3.5 hours (mammalian reticulocytes, in vitro),10 min (yeast, in vivo), and >10 hours (Escherichia coli, in vivo). The Polytope binds with four broadly neutralizing antibodies of B7, C8, A11, and C10 (bnAbs) which estimated that four bnAbs can recognize four serotypes of dengue virus. The designed polytope has prospect to produce in Escherichia coli and can be applied as vaccine of heterotypic dengue virus serotype. Polytope is potentially able to generate humoral and cellular immunity.

BackgroundEpstein-Barr virus (EBV) can cause cancer in people from around the world. There is no EBV vaccine available for use on a global scale. However, emerging evidence suggests that the epitope on the gp350/220 capsid protein may be developed into an EBV vaccine. Nevertheless, the production of small, single epitope is challenging of stability issues and possible alteration of peptide structure. In this study, a tandem epitope was developed consisting of three single epitopes, aimed to improve stability, antigenicity and preserve epitope structure.Materials and methodsA tandem epitope was designed using bioinformatics based on the epitope structure of the gp350/220 protein. The tandem epitope structure was analyzed using a protein folding method with Abalone software, which was further refined via YASARA force field and molecular repairing using a FoldX method. Immunogenicity was examined with Epitopia software, whereas allergen properties were tested using AlgPred. The pattern of the tandem epitope binding with anti-gp350/220 antibodies was performed using Z-dock and snugDock. The tandem epitope was then overproduced in E. coli strain BL21 as a host cell.ResultOur model demonstrated a successfully designed and overproduced tandem epitope. The tandem epitope demonstrated a similar structure compared with the epitope of whole protein gp350/220. Our epitope also demonstrated non-allergen and antigenicity properties, and possessed antibody binding patterns consistent with whole protein gp350/220.Conclusion and recommendationThese data suggest a novel tandem epitope composed of three similar epitopes demonstrates antigenicity, structure, and binding properties consistent with whole protein gp350/220. We also demonstrate successful production of the tandem epitope using E. coli strain BL21 as a host. Future in vivo experimental animal research is necessary to test the ability of this tandem epitope to stimulate antibody production.

Objectives Dengue virus surface proteins are often used in the development of vaccines that protect against dengue virus infection. However, the surface proteins on the four serotypes of dengue virus display high variation, which increases the difficulty of developing a vaccine that can protect against all viral strains. In this study, a polytope that is recognized by broadly neutralizing antibodies (bnAbs) was designed using conserved epitopes from the four serotypes. Methods We constructed a polytope using four conserved dengue virus epitopes such that two aligned epitopes were separated from the other two epitopes by a histidyl-tRNA synthetase spacer. The epitopes were selected based on our previous docking studies. We then performed molecular docking of the polytope with the four bnAbs. Results The polytope bound precisely to the four bnAbs—B7, C8, A11, and C10. Moreover, the polytope had a higher affinity for the bnAbs compared to the DENV2 antigen. The polytope and A11 antibody complex had the lowest binding energy relative to complexes between the polytope and the other three antibodies assessed. The highest total number of hydrogen bonds was found in the polytope and B7 antibody complex. The hydrogen bond length in all the complexes ranged from 2.07 to 3.03 Å, implying that hydrogen bonds stabilized the complexes. Conclusion The developed polytope interacted with four different bnAbs that recognize the four serotypes of dengue virus. The results of this study suggest that this polytope warrants further development for use in a broad-spectrum vaccine against dengue virus.

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