Balance of infection-enhancing and neutralizing antibodies induced by a dengue tetravalent DNA vaccine in a mouse model

Most dengue vaccines currently under development are designed to induce neutralizing antibodies. Although neutralizing antibodies are believed to be protective, most of the antibody species that have neutralizing activities also have infection-enhancing activities at subneutralizing doses. Thus, the balance of neutralizing and enhancing activities induced by a dengue tetravalent vaccine was analyzed in this study in a DNA vaccine model using mice. The balance was measured using semi-adherent K562 cells in an assay system we previously developed. This system detected enhancing activities in sera from mice immunized with the vaccine when complement was absent from the virus-antibody mixture in this assay. Mice passively transferred with vaccinated mouse sera or monoclonal antibodies that possessed neutralizing activities as determined on Vero cells, also showed enhancing activities in their sera during the course of antibody waning in the absence of complement. However, these enhancing activities were abolished or altered to neutralizing activities in the presence of complement in our assay system, except in mice passively transferred with a monoclonal antibody of isotype IgG1. Thus, enhancing activities were not shown in mice immunized with a DNA vaccine as far as complement was included in our in vitro assay system.