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 r estricted to certain subclasses depending on the nature of the immunog en. Immunization with live viruses generally leads to a predominant Ig G2a response, which may be the most effective at resisting future chal lenge due to the unique effector functions of IgG2a. Knowledge of subc lass responses following immunization with dengue vaccine candidates m ay be helpful in determining which candidates are most efficacious. We measured the dengue-specific IgG subclass responses of BALB/c mice fo llowing immunization with live dengue-2 virus or with a partially puri fied recombinant dengue-2 envelope (E) protein. Subclass responses fol lowing immunization with live virus were IgG2a > IgG1 > IgG2b > IgG3, as opposed to IgG1 > IgG2a > IgG2b > IgG3 after immunization with reco mbinant protein. Responses of all subclasses except IgG1 were greater following immunization with live dengue than with the recombinant E pr otein. Neutralizing antibody titers were also higher after immunizatio n with live virus than with E protein and were positively correlated w ith dengue-specific IgG2a responses in mice immunized with recombinant E protein. Following separation of the four IgG subclasses by chromat ography, the IgG2a fraction exhibited the greatest neutralizing activi ty. The results seen after immunization with live dengue virus or reco mbinant E protein in this study are in concordance with studies involv ing other viruses and viral proteins and may have implications for the development of an effective vaccine for dengue.