Compatibility of plasmids expressing different antigens in a single DNA vaccine formulation

One anticipated advantage of DNA immunization is the potential to create mu ltivalent vaccines. We have examined the effects of mixing plasmids into si ngle formulations using plasmids expressing four different membrane bound g lycoproteins from bovine herpesvirus-l (BHV-1), bovine parainfluenzavirus-3 (bPI3) and human influenza virus (HINF), Plasmids were delivered by intrad ermal injection into the tails of mice and the types of responses generated were clearly affected by the expressed antigen. Plasmids expressing glycop roteins B and D of BHV-1, and the haemagglutinin/neuraminidase of bPI3, gen erated responses with a predominance of IgG1, suggestive of a Th2 type of r esponse, In contrast, the plasmid expressing HINF haemagglutinin induced an antibody response biased towards IgG2a, indicating a Th1 type of response. In most instances the mixing of plasmids had only slight effects on the ma gnitude or bias of the responses to the individual components. However, und er certain conditions we found that addition of a second plasmid converted an IgG2a biased response to a response with primarily IgG1 antibody. The re verse situation (i.e. an IgG1 conversion to IgG2a), however, was not found. These findings have important implications for the development of multival ent vaccines.