Cytokine-Containing Liposomes as Adjuvants for HIV Subunit Vaccines

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Abstract
Dehydration-rehydration liposome vesicles (DRVs) containing various cytokines were evaluated for their ability to induce delayed-type hypersensitivity (DTH) and humoral immunity to the recombinant envelope protein rgp120 of the MN strain of human immunodeficiency virus type 1 (HIV-1). The DRVs trapped ∼25% of the radiolabeled cytokines and ∼17% of the radiolabeled rgp120 that were added. The level of trapping was greater than the aqueous volume of the DRVs, indicating association of the proteins with the lipid bilayer. Flow cytometric analysis using antibody to rgp120 or the V3 loop of rgp120 showed the diameter of the DRVs to be 2–7.5 μm. Transmission electron microscopy confirmed the heterogeneity in size of the DRVs and revealed morphological heterogeneity. Transmission electron microscopy with immunogold labeling also revealed the presence of rgp120 on the surface of the DRVs. In vitro bioassays demonstrated slow leakage of biologically active cytokines from DRVs soaked in tissue culture medium containing serum. Mice injected subcutaneously three times at 14-day intervals with DRVs containing 15 μg of rgp120 plus interleukin 6 (IL-6) or interferon γ (IFN-γ) produced significantly greater DTH responses than mice injected with DRVs containing rgp120 alone. Soluble rgp120 plus soluble IFN-γ produced DTH in some experiments, but of lower magnitude than the comparable DRVs. Interleukin 6, but not IFN-γ, increased the antibody titer to rgp120 when included in the DRVs. The mice did not develop antibodies to IFN-γ or IL-6. Induction of DTH by vaccines may increase protection from viral pathogens such as HIV. Cytokine-containing liposomes may be an effective adjuvant for the induction of a DTH response to envelope-antigen subunit vaccines.