Synergistic Interactions of Anti-NSl Monoclonal Antibodies Protect Passively Immunized Mice from Lethal Challenge with Dengue 2 Virus

Non-neutralizing, serotype-specific anti-NS1 monoclonal antibodies partially protected passively immunized mice from lethal dengue 2 virus intracerebral challenge. There was no apparent correlation between complement-fixing activity and protective capacity among individual anti-NS1 monoclonal ntibodies. Immunization with specific ombinations ofnon-protective or partially protective antibodies resulted in prolonged survival or reduced mortality. Solid protection, equal to that achieved after immunization with neutralizing polyclonal antibody, was achieved only with an antibody pair which individually fixed complement to high titre with homologous virus. Some groups of mice had increased morbidity after immunization with combinations of protective monoclonal antibodies that bind to overlapping epitopes. These results may affect he design of recombinant dengue vaccines which may require the inclusion of serotype-specific antigenic domains. Previous tudies have established the importance of the humoral response for survival after lethal flavivirus challenge (Monath, 1986). However, the functional characteristics of the antibodies required for protection remain u clear. While neutralizing antibodies against he envelope (E) glycoprotein have been regularly associated with immunity to flavivirus infections, a lack of correlation between protection and heterologous neutralizing antibody levels has bee