A simple method for evaluating dengue vaccine effectiveness in mice based on levels of viremia caused by intraperitoneal injection of infected culture cells

Abstract

A simple dengue vaccine evaluation system was established using a model of dengue type 2 virus (DENV2) infection in immunocompetent mice. Mice are usually non-permissive hosts, and artificial viremia was therefore created by intraperitoneal injection of K562 cells infected with DENV2. Plasma virus titers were approximately 4-5log(10) focus-forming units/ml at 10h after injection of 1x10(7) K562 cells into ICR, ddY and BALB/c mice. ICR mice immunized with an experimental vaccine against DENV2 showed reduced levels of viremia, associated with neutralizing antibody titers. Similarly, ICR mice passively immunized with purified IgG fractions of monoclonal antibodies possessing neutralizing activities also had reduced levels of viremia. However, the degree of viremia reduction differed according to the antibody species. Although some mice developed neurologic symptoms and/or died within 21 days of K562 injection, viremia reduction was considered to be a reliable indicator of the protective capacities of candidate dengue vaccines.