Designing a polytope for use in a broad-spectrum dengue virus vaccine

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.