MURINE IMMUNOGLOBULIN-G SUBCLASS RESPONSES FOLLOWING IMMUNIZATION WITH LIVE DENGUE VIRUS OR A RECOMBINANT DENGUE ENVELOPE PROTEIN

Murine immunoglobulin G (IgG) subclass responses to immunization are restricted to certain subclasses depending on the nature of the immunogen. Immunization with live viruses generally leads to a predominant IgG2a response, which may be the most effective at resisting future challenge due to the unique effector functions of IgG2a. Knowledge of subclass responses following immunization with dengue vaccine candidates may be helpful in determining which candidates are most efficacious. We measured the dengue-specific IgG subclass responses of BALB/c mice following immunization with live dengue-2 virus or with a partially purified recombinant dengue-2 envelope (E) protein. Subclass responses following immunization with live virus were IgG2a > IgG1 > IgG2b > IgG3, as opposed to IgG1 > IgG2a > IgG2b > IgG3 after immunization with recombinant protein. Responses of all subclasses except IgG1 were greater following immunization with live dengue than with the recombinant E protein. Neutralizing antibody titers were also higher after immunization with live virus than with E protein and were positively correlated with dengue-specific IgG2a responses in mice immunized with recombinant E protein. Following separation of the four IgG subclasses by chromatography, the IgG2a fraction exhibited the greatest neutralizing activity. The results seen after immunization with live dengue virus or recombinant E protein in this study are in concordance with studies involving other viruses and viral proteins and may have implications for the development of an effective vaccine for dengue.