Murine Immunoglobulin G Subclass Responses Following Immunization with LiveDengue Virus or a Recombinant Dengue Envelope Protein

摘要

Murine IgG subclass responses to immunization differ depending on the nature ofthe 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 developed a Particle Concentration Fluorescent Immunoassay to quantify the dengue-specific IgG subclass responses of BAtB/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 > IgGl > IgG2b IgG3, as opposed to IgGi IgG2a > IgG2b IgG3 after recombinant protein. Responses of all subclasses except IgGi were greater following immunization with live dengue than with the recombinant E protein. Plaque reduction neutralization tests demonstrated higher antibody titers after immunization with live virus than with E protein; titers were also positively correlated with dengue-specific IgG2a responses in those mice immunized with recombinant E protein. Following separation of the four subclasses by Protein A 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 may have implications for the development of an effective vaccine for dengue.