The present invention provides adjuvants, vaccines and therapies in which antigen presentation is enhanced through inhibition of negative immune regulators. The compositions and methods are useful for generating immune responses against antigens, including microbial pathogens and tumor-associated antigens, by way of inhibiting a negative immune regulator in a cell and providing a proinflammatory stimulus. In particular, nucleotides encoding inhibitors of negative immune regulators, antigens, and co-stimulatory molecules are contacted with immune cells in order to elicit a therapeutic or prophylactic response.
