Enhancement of immune responses to an HIV gp120 DNA vaccine by fusion to TNF alpha cDNA

DNA vaccines have considerable potential for disease prophylaxis and therapy, but are generally poorly immunogenic. A number of means of enhancing immunogenicity have been assessed, including the co-expression of cytokines, the use of heterologous prime-boost regimes, and the addition of more conventional adjuvants. In this study we have assessed the effects on gp120 DNA immunogenicity of in-frame fusion of tumor necrosis factor alpha DNA to DNA encoding a large fragment of HIV gp120. The studies were performed using a DNA prime, protein boost regime and a heterologous boosting protein. Fusion of TNFα DNA enhanced Th1 related immune responses against both the priming and the boosting gp120. In-frame fusion of interferon gamma-encoding DNA at the 5′ end of the chimeric molecule, to create a tripartite fusion, had no additional effect on immunogenicity.