Human immunodeficiency virus type‐1‐specific immune responses induced by DNA vaccination are greatly enhanced by mannan‐coated diC14‐amidine

Abstract

Use of mannan‐coated N‐t‐butyl‐N′‐tetradecyl‐3‐tetradecylamino‐propion‐amidine (diC14‐amidine) as an adjuvant for a DNA vaccine encoding glycoprotein 160 of human immunodeficiency virus type‐1 (HIV‐1) enhanced the antigen‐specific immune responses. The role of interferon‐γ (IFN‐γ) and interleukin‐12 in the mechanism of adjuvant action was also evaluated. Coating of diC14‐amidine with mannan significantly augmented the HIV‐specific delayed‐type hypersensitivity reaction induced by the immunogenic DNA. HIV‐1‐specific cytotoxic T lymphocyte activity was also markedly enhanced by the mannan‐diC14‐amidine cocktail. An immunomodulatory effect of this cocktail was inhibited by treatment with anti‐IFN‐γ monoclonal antibody in vivo, which suggests that IFN‐γ 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 elicits Th1‐biased immune responses.