Siew-Yen Chong, Michael A. Egan, Michele A. Kutzler, Shakuntala Megati, Amjed Masood, Vidia Roopchard, Dorys Garcia-Hand, David C. Montefiori, Jorge Quiroz, Margherita Rosati, Eva B. Schadeck, Jean D. Boyer, George N. Pavlakis, David B. Weiner, Maninder Sidhu, John H. Eldridge, Zimra R. Israel

Plasmid-based IL-12 has been demonstrated to successfully enhance the immunogenicity of DNA vaccines, thus enabling a reduction of the amount of DNA required for immunization. IL-15 is thought to affect the maintenance and enhance effector function of CD8(+) memory T cells. Since the ability to elicit a long-term memory response is a desirable attribute of a prophylactic vaccine, we sought to evaluate the ability of these plasmid-based cytokines to serve as vaccine adjuvants in rhesus macaques. Macaques were immunized with plasmid DNA encoding SIVgag in combination with plasmid IL-12, IL-15, or a combination of IL-12 and IL-15. The plasmid-based cytokines were monitored for their ability to augment SIVgag-specific cellular and humoral immune responses and to alter the clinical outcome following pathogenic SHIV(89.6P) challenge. Macaques receiving SIVgag pDNA in combination with plasmid IL-12 alone, or in combination with plasmid IL-12 and IL-15, demonstrated significantly elevated cell-mediated and humoral immune responses resulting in an improved clinical outcome following virus challenge compared to macaques receiving SIVgag pDNA alone. Macaques receiving SIVgag pDNA in combination with plasmid IL-15 alone demonstrated minor increases in cell-mediated and humoral immune responses, however, the clinical outcome following virus challenge was not improved. These results have important implications for the continued development of plasmid DNA vaccines for the prevention of HIV-1 infection.