Enhanced type I immune response to a hepatitis B DNA vaccine by formulation with calcium- or aluminum phosphate

DNA vaccines induce protective humoral and cell-mediated immune responses i n several animal models. When compared with conventional vaccines, however, DNA vaccines often induce lower antibody titers. We have now found that fo rmulation of a DNA vaccine encoding hepatitis B surface antigen with calciu m- or aluminum phosphate adjuvants can increase antibody titers by 10-100-f old and decrease the immunogenic dose of DNA by 10-fold. Furthermore, boost ing an HBs protein-primed response With the adjuvanted DNA vaccine resulted in a dramatic increase in the HBs-specific IgG2a response reflecting a shi ft towards a TH1 response. The mechanism by which aluminum phosphate exerts its adjuvant effect is not through increased expression of HBsAg in vivo; rather, the adjuvant appears to increase the number and affinity of HBs pep tide antigen-specific IFN-gamma and IL-2 secreting T cells. (C) 2000 Elsevi er Science Ltd. All rights reserved.