title: Evaluation of chimeric DNA vaccines consisting of premembrane and envelope genes of Japanese encephalitis and dengue viruses as a strategy for reducing induction of dengue virus infection-enhancing antibody response.
abstract: 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.
authors.affiliation: Department of Vaccinology, Center for Infectious Diseases, Kobe University Graduate School of Medicine.
authors.forename: Fithriyah
authors.initials: F
authors.lastname: Sjatha
authors.forename: Miwa
authors.initials: M
authors.lastname: Kuwahara
authors.forename: T Mirawati
authors.initials: TM
authors.lastname: Sudiro
authors.forename: Masanori
authors.initials: M
authors.lastname: Kameoka
authors.forename: Eiji
authors.initials: E
authors.lastname: Konishi
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D016466:CHO Cells; D002460:Cell Line; D003412:Cricetulus; D003715:Dengue / Q000276:immunology*; D053059:Dengue Vaccines / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D018349:Encephalitis Viruses, Japanese / Q000145:classification / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012703:Serotyping; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D053059:Dengue Vaccines; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins
keywords: Antibody-dependent enhancement; chimera; dengue; vaccine