Nucleic acid vaccination has many potential advantages over traditional methods, but suffers from the fact that DNA vaccines tend to be relatively poorly immunogenic. Attempts to enhance DNA vaccine immunogenicity have included the addition of cytokine-encoding plasmids into the formulation, as well as the use of heterologous prime-boost regimes and the addition of conventional adjuvants, such as alum. We have previously shown that interferon gamma fusions have enhanced immunogenicity as recombinant protein vaccines. We have assessed here the immunogenicity of an interferon gamma-gp120 fusion delivered as a DNA vaccine, in the context of a prime-boost strategy and in the presence of absence of aluminium phosphate. Fusion of gp120 DNA to interferon gamma-encoding DNA resulted in strongly enhanced priming, especially of Th1 responses, including IgG2a responses to a protein boost.