INTRANASAL ADMINISTRATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) DNA VACCINE WITH INTERLEUKIN-2 EXPRESSION PLASMID ENHANCES CELL-MEDIATED-IMMUNITY AGAINST HIV-1

DNA vaccine against human immunodeficiency virus type-1 (HIV-1) can in duce substantial levels of HIV-1-specific humoral and cell-mediated im munity. To develop more potent HIV-I DNA vaccine formulations, we used a murine model to explore the immunomodulatory effects of an interleu kin-2 (IL-2) expression plasmid on an HIV-1 DNA vaccine following intr anasal administration of the combination. When the vaccine and express ion plasmid were incorporated into cationic liposomes and administered to mice, the HIV-1-specific delayed-type hypersensitivity response an d cytotoxic T lymphocyte activity were significantly increased. Restim ulated immune lymphoid cells showed enhanced production of both IL-2 a nd interferon-gamma and reduced secretion of IL-4. The level of total antibody to HIV-1 antigen was not greatly changed by coadministration of the DNA vaccine and IL-2 expression plasmid. An analysis of serum H IV-1-specific IgG subclasses showed a significant drop in the IgG1/IgG 2a ratio in the group that received the plasmid-vaccine combination. T hese results demonstrate that the IL-2 expression plasmid strongly enh ances the HIV-1-specific immune response via activation of T helper ty pe-1 cells.