| Title | Recombinant Protein Mimicking the Antigenic Structure of the Viral Surface Envelope Protein Reinforces Induction of an Antigen‑Specific and Virus‑Neutralizing Immune Response Against Dengue Virus |
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| Author | Ju Kim1, Tae Young Lim2, Jisang Park1,2, and Yong‑Suk Jang1,2,3* |
| Address | 1Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju 54896, Republic of Korea, 2Innovative Research and Education Center for Integrated Bioactive Materials and the Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju 54896, Republic of Korea, 3Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, Republic of Korea |
| Bibliography | Journal of Microbiology, 61(1),131-143, 2023, |
| DOI | 10.1007/s12275-023-00021-z |
| Key Words | Antigen · Dengue virus · Epitope · Neutralization · Vaccine |
| Abstract | Dengue virus (DENV), belonging to the family Flaviviridae, is the causative agent of dengue and comprises four serotypes. A second heterologous DENV infection is a critical risk factor for severe dengue, and no effective vaccine is available to prevent infection by all four DENV serotypes. Recombinant DENV vaccines are primarily based on the envelope proteins, prM and E. The E protein and its envelope domain III (EDIII) have been investigated as candidate antigens (Ags) for recombinant subunit vaccines. However, most EDIII-based Ags are monomers that do not display the cognate antigenic structure of E protein, which is essential for induction of virus-neutralizing immunity. Here, we developed recombinant DENV-2 envelope domain (r2ED) protein as an Ag that mimics the quaternary structure of E protein on the DENV surface. We confirmed that r2ED retained the conformational epitope displayed at the E-dimer interface, which reportedly exhibits broad virus-neutralizing capacity, without displaying the fusion loop epitope that causes antibody (Ab)-dependent enhancement. Furthermore, compared with EDIII alone, r2ED elicited stronger Ag-specific and cross-reactive neutralizing Ab and T cell-mediated immune responses in mice. This Ag-specific immunity was maintained at an elevated level 6 months after the last immunization, suggesting sustained Ag-specific immune memory. Taken together, these observations suggest that r2ED could be used to develop an improved subunit vaccine capable of inducing a broadly cross-reactive and long-lasting immune response against DENV infection. |