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The development of a dengue virus vaccine is a major priority in efforts to control the diseases. Several researchers are currently using the Asian 1 and Asian 2 genotypes as vaccine candidates for dengue type 2 virus (DENV-2). However, in this study, we constructed a recombinant plasmid-based prM/E gene, from a DENV-2 Cosmopolitan genotype strain as a dengue DNA vaccine candidate. The protein expression of the recombinant plasmid in CHO cells was analyzed using an enzyme-linked immunosorbent assay, western blotting, and sucrose gradient sedimentation. After being used to immunize ddY mice three times at doses of 25 or 100 μg, the DNA vaccine induced humoral immune responses. There was no difference in the neutralizing antibody titer (focus reduction neutralization test 50% value) of mice immunized with 25 and 100 μg DNA vaccine doses. When challenged with 3 × 10(5) FFU DENV-2, immunized mice could raise anamnestic neutralizing antibody responses, which were observed at day 4 and day 8 post-challenge. Analysis of immunogenicity using BALB/c mice showed that their antibody neutralization titers were lower than those of ddY mice. In addition, the antibodies produced after immunization and challenge could also neutralize a DENV-2 Asian 2 genotype (New Guinea C) strain. Therefore, the DENV-2 Cosmopolitan genotype may be a DENV-2 vaccine candidate.

Neutralizing antibodies induced by dengue virus (DENV) infection show viral infection-enhancing activities at sub-neutralizing doses. On the other hand, preimmunity against Japanese encephalitis virus (JEV), a congener of DENV, does not increase the severity of DENV infection. Several studies have demonstrated that neutralizing epitopes in the genus Flavivirus are mainly located in domain III (DIII) of the envelope (E) protein. In this study, chimeric premembrane and envelope (prM-E) gene-based expression plasmids of JEV and DENV1 with DIII substitution of each virus were constructed for use as DNA vaccines and their immunogenicity evaluated. Sera from C3H/He and ICR mice immunized with a chimeric gene containing DENV1 DIII on a JEV prM-E gene backbone showed high neutralizing antibody titers with less DENV infection-enhancing activity. Our results confirm the applicability of this approach as a new dengue vaccine development strategy., (© 2014 The Societies and Wiley Publishing Asia Pty Ltd.)