Antigenic analysis of dengue virus using monoclonal antibodies

Dengue viruses are classified as a separate antigenic group within the Flaviviridae on the basis of cross-reactivity in neutralization assays employing polyclonal sera. Additional serological relationships defining group, complex and type specificity between members of the various antigenic groups have also been identified with polyclonal sera in analyses using hemagglutination inhibition (HI) and complement fixation (CF) tests. With the advent of monoclonal antibodies, however, this picture has become far more complex. While the basic framework of serological relationships has been confirmed, a large number of additional cross-reactivities have been identified that suggest a much greater degree of antigenic diversity and/or relatedness than previously imagined. Monoclonal antibodies have not only been used to dissect the antigenic relatedness between flaviviruses but also in studies aimed at defining epitopes on viral proteins involved in a range of biological activities from protection to antibody-dependent enhancement (ADE) of infection. Of the ten proteins encoded by the dengue virus genome, monoclonal antibodies have been raised to six, including each of the structural proteins (C, prM, E) and three of the non-structural proteins (NS1, NS3, NS5). These antibodies have been applied to the construction of functional maps and in particular to the definition of antigenic determinants involved in protection.