DNA inoculations with HIV-1 recombinant genomes that express cytokine genes enhance HIV-1 specific immune responses

Abstract

Vaccination with HIV-1 DNA sequences induce both humoral and cellular immune responses in experimental animals. However, these responses are relatively weak and are often only transient in their nature. In order to enhance the level of HIV-1 specific immunity, we have engineered HIV-1 DNA constructs which contained various cytokine genes such as interleukin-2 (IL-2), granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) gene. These constructs have deleted the tat and nef genes of HIV-1 to eliminate their immunosuppressive effects. Immunizations with these recombinant constructs elicited moderate proliferative T cell responses but poor antibody responses in rats. However, inoculations of HIV-I DNA that contained the GM-CSF or the IL-2 gene significantly enhanced humoral and proliferative T cell responses, respectively. Thus, recombinant HIV-1 genomes such as those described here may increase the efficacy of DNA vaccination. (C) 1999 Elsevier Science Ltd. All rights reserved.