Effect of chemical adjuvants on DNA vaccination

DNA vaccination is useful for generating immune responses, particularly the cell-mediated immune response, in a wide variety of species. However, DNA vaccination generally induces only relatively weak responses; hence, various approaches have been developed recently in order to improve its efficacy or immunopotency. The use of a chemical adjuvant is one of them. Previously we have shown that Bupivacaine or Marcaine can modulate immune responses induced by DNA vaccines [Proc. Natl. Acad. Sci. 90 (1993) 4156]. Following that lead, we have recently tested several additional chemicals for their usefulness as adjuvants in DNA inoculation. Of a total of five chemicals tested, levamisole exhibited strongest Th1 stimulatory activity whereas Tween 80 showed weakest Th1 activity, as determined by IgG2a production, and saline formulation induced weak T cell proliferation and DTH, in animals inoculated with a DNA construct expressing the foot-mouth disease viral capsule protein VP1. Furthermore, co-inoculation of levamisole increased the production of IFN-gamma by more than 100-fold as compared to that by DNA inoculation formulated in saline. In contrast, a previously reported chemical adjuvant, bupivacaine, stimulated only modest levels of overall antibody production, with relatively low level of Ig2a. These results demonstrate the usefulness of various chemicals, particularly levamisole, for modulating the outcome of DNA vaccination, in both the intensity of the immune response and the polarity of such response (toward Th1).