       Document 0593
 DOCN  M9630593
 TI    Cytokine-containing liposomes as adjuvants for HIV subunit vaccines.
 DT    9603
 AU    Lachman LB; Shih LC; Rao XM; Hu X; Bucana CD; Ullrich SE; Cleland JL;
       Department of Cell Biology, University of Texas M.D. Anderson; Cancer
       Center, Houston 77030, USA.
 SO    AIDS Res Hum Retroviruses. 1995 Aug;11(8):921-32. Unique Identifier :
       AIDSLINE MED/96020093
 AB    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 approximately 25% of the radiolabeled
       cytokines and approximately 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 microns. 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 micrograms of rgp120 plus interleukin
       6 (IL-6) or interferon gamma (IFN-gamma) produced significantly greater
       DTH responses than mice injected with DRVs containing rgp120 alone.
       Soluble rgp120 plus soluble IFN-gamma produced DTH in some experiments,
       but of lower magnitude than the comparable DRVs. Interleukin 6, but not
       IFN-gamma, increased the antibody titer to rgp120 when included in the
       DRVs. The mice did not develop antibodies to IFN-gamma 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.
 DE    Adjuvants, Pharmaceutic/*ADMINISTRATION & DOSAGE  Animal
       Cytokines/*ADMINISTRATION & DOSAGE  Drug Carriers  Female  Human
       Hypersensitivity, Delayed/CHEMICALLY INDUCED/*IMMUNOLOGY  HIV Envelope
       Protein gp120/*ADMINISTRATION & DOSAGE  HIV
       Infections/*IMMUNOLOGY/PREVENTION & CONTROL  *HIV-1  Liposomes  Mice
       Mice, Inbred C3H  Support, U.S. Gov't, P.H.S.  Vaccination  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

