Recombinant protein mimicking the antigenic structure of the envelope protein of dengue virus enhances antigen-specific virus-neutralizing immune response induction

Abstract

Abstract Dengue virus (DENV) comprises four serotypes in the family Flaviviridae and infects approximately 390 million people worldwide every year. So far, there is no effective therapy available for dengue diseases other than supportive care. Therefore, the development of safe and effective vaccines is critical. Most of DENV vaccines are primarily based on the envelope proteins prM and E, which are believed to induce protective immune responses in humans. Particularly, the DENV E protein and its envelope domain III (EDIII) have been investigated as candidate antigens for recombinant subunit vaccine. However, most EDIII-based antigens do not display quaternary structure of DENV E protein which is essential to induce virus neutralizing immune responses. We developed the Recombinant of DENV-2 Envelope Domain (r2ED) as an antigen, which mimics the antigenic structure of E protein on the surface of DENV. We tested the ability of r2ED to boost antigen-specific immune response induction in vivo. As a result, we observed that r2ED elicited antigen-specific and neutralizing antibody responses and T cell-mediated immune responses higher than EDIII alone in mice. In addition, antigen-specific antibody and T cell responses were maintained in an enhanced level at 6 months after the last immunization in r2ED-immunized mice, suggesting the sustained immune memory responses for a long time. These results are helpful to develop the improved subunit vaccine for inducing an effective and long-lasting immune response against DENV infection. This work was supported by the NRF funded by the Ministry of Education No. 2017R1A6A1A03015876 and the Ministry of Science and ICT No. 2020K1A4A7A02095058. J. Park, J. Kim, and S. Cho were supported by the BK21 FOUR program in the Department of Bioactive Material Sciences.