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1996-02-27
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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).