BIKEN Endowed Department of Dengue Vaccine Development was established in Faculty of Tropical Medicine, Mahidol University, Thailand, in 2011 by endowment from The Research Foundation for Microbial Diseases of Osaka University, Osaka, Japan to Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Dengue fever is the most important mosquito-borne viral disease, which is distributed in tropical regions and producing an estimated 300,000 patients daily. Dengue hemorrhagic fever is its severer form and has a mortality up to 20% if an appropriate treatment is not done. Unfortunately, no approved vaccines or specific antivirals have been developed.
Our department will carry out basic research studies on (1) mechanisms involved in pathogenesis of dengue fever and dengue hemorrhagic fever, (2) virulence, transmission and evolution of dengue viruses, and (3) dengue vaccine development using several strategies.
|World-first efficacy trial for evaluating a candidate dengue vaccine suggested a need to improve the current neutralization test using Vero cells recommended by WHO. We have established an antibody assay system using K562 cells bearing Fcγ receptors to seek more accurate antibody levels required for disease protection. A patient sample showed neutralizing activity with dengue type 1 virus-infected cell counts <103 PFU/ml and enhancing activity with infected cell counts >103 PFU/ml depending on dilution factor as shown above. The assay also indicated the presence of both complement-dependent and independent antibodies.||Most mouse monoclonal antibodies generated using dengue type 1 virus antigen displayed both neutralizing and enhancing activities depending on concentration (NEAb), whereas some showed only enhancing (EAb) or neutralizing activities (NAb). One obstacle hampering dengue vaccine development is a concern of deterioration caused by vaccine-induced enhancing antibodies. An antigen possessing epitopes that can effectively induce NAb should contribute to development of a safe and efficacious dengue vaccine.|