Characterization and modulation of immune responses in mice to a DNA-based vaccine

by Lewis, P. Jeffrey

DNA-based vaccines represent a novel method of immunization that has been demonsaated to induce immune responses in anunals, using a variety of antigens and methods of vaccine delivery. More recently, modulation of immune responses to DNA vaccines has been studied through codelivay of plasrnids encoding a number of different murine cytokines. Moa recently scientists have assessed the abiliy of these novel vaccines to overcome certain problems associated with immunization of passively immune young animais. We characterized the immune response to several DNA-based vaccines encoding intraceliular, extracellularand membrane anchored foms of glycoprotein D (gD), an immunodominant antigen, f7om the viral envelope of the bovine herpesvinis- 1 (BHV-1 ). BHV- 1 is an economicaiiy important respiratory pathogen of cattle which is responsible for infectious bovine rhinomcheitus, genitai infection, abortion and is also the immunosuppressive p m pathogen of the shipping fever complex We noted that the kinetics of gD-specific senun antibody development was delayed if the antigen was expressed inside the cell (cytosolic) as compared to expression outside the ce11 (plasma membrane anchored or semeted) It was also noted kat most mice immunized with plasmids encoding secreted, ce11 dace or cytosolic, versions of gD displayed significant levels of anti-gD antibody, in sera, at 5 and 1/2 months post immunization. Indeed, some mice showed maintenance, or increases, in senun ELISA titers at 5 and 1/2 months poa immunkation. Intrarnusdar injection witb plasmids encoding secreted or celi associated fom of BHV-1 gD resulted in a predominance of splenic EN y consistent with a Th- 1 type of immune response. Surpnsingly, despite the involvement of IFN y in the isotype switch to IgG, only mice receiving plasmids encoding the ce11 associated (plasma membrane anchored and cytosolic) displayed a predominance of this isotype. Mice irnmunized with plasmids encoding the secreted fom of gD displayed a predominance of serum IgG,. Using cytokine and antiiody forming ce11 (MC)