Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination

With accumulating evidence indicating the importance of cytotoxic T Lymphoc ytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replicatio n in infected individuals, strategies are being pursued to elicit virus-spe cific CTLs with prototype HIV-1 vaccines. Here, we report the protective ef ficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccine s expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administra tion of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (I L-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL -2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak C TL responses, rapid Loss of CD4(+) T cells, no virus-specific CD4(+) T cell responses, high setpoint viral loads, significant clinical disease progres sion, and death in half of the animals by day 140 after challenge. in contr ast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4(+) T cell counts, preserved virus-specific CD4(+) T cell responses, Low to unde tectable setpoint viral Loads, and no evidence of clinical disease or morta lity by day 140 after challenge.