HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-SPECIFIC IMMUNE-RESPONSES INDUCEDBY DNA VACCINATION ARE GREATLY ENHANCED BY MANNAN-COATED DIC14-AMIDINE

Use of mannan-coated tyl-N'-tetradecyl-3-tetradecylamino-propionamidin e (diC14-amidine) as an adjuvant for a DNA vaccine encoding glycoprote in 160 of human immunodeficiency virus type-1 (HIV-1) enhanced the ant igen-specific immune responses. The role of interferon-gamma (IFN-gamm a) and interleukin-12 in the mechanism of adjuvant action was also eva luated. Coating of diC14-amidine with mannan significantly augmented t he HIV-specific delayed-type hypersensitivity reaction induced by the immunogenic DNA. HIV-1-specific cytotoxic T lymphocyte activity was al so markedly enhanced by the mannan-diC14-amidine cocktail. An immunomo dulatory effect of this cocktail was inhibited by treatment with anti- IFN-gamma monoclonal antibody in vivo, which suggests that IFN-gamma, plays an important role in inducing cell-mediated immunity by the DNA vaccine containing this adjuvant. The results of both antigen-specific immunoglobulin isotype analysis and cytokine measurement showed that the immunogenic DNA incorporated into mannan-coated diC14-amidine elic its Th1-biased immune responses.