Cytokine-containing liposomes as adjuvants for HIV subunit vaccines.
Cytokine-containing liposomes as adjuvants for HIV subunit vaccines.
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含有细胞因子的脂质体作为 HIV 亚单位疫苗的佐剂。
DOI：
10.1089/aid.1995.11.921
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Cleland,JL
中科院分区：
文献类型：
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作者：
Lachman,LB;Shih,LC;Rao,XM;Hu,X;Bucana,CD;Ullrich,SE;Cleland,JL
研究了含有多种细胞因子的脱水-再水化脂质体囊泡(DRV)对人类免疫缺陷病毒1型(HIV-1)MN株重组包膜蛋白rgp120的诱导迟发型超敏反应(DTH)和体液免疫的能力。DRV捕获了所添加的放射性标记细胞因子∼的25%和放射性标记Rgp120的∼17%。捕获水平大于DRV的水体积，表明蛋白质与脂质双层结合。用rgp120抗体或rgp120的V3环进行的流式细胞仪分析显示，DRV的直径为2~7.5mRV，透射电子显微镜证实了DRV的大小不均一，并显示了形态上的异质性。免疫金标记法的透射电子显微镜也显示DRV表面存在rgp120。在体外生物检测中发现，浸泡在含有血清的组织培养液中的DRV具有生物活性的细胞因子缓慢渗漏。小鼠皮下注射含15μg rgp120的DRV加白细胞介素6(IL-6)或干扰素γ(干扰素-γ)，每隔14天皮下注射3次，其迟发型超敏反应明显高于单独注射rgp120的小鼠。可溶性rgp120和可溶性干扰素-γ在某些实验中产生迟发型超敏反应，但幅度低于可比的DRV。白介素6，而不是干扰素-γ，当包括在DRV中时，提高了rgp120的抗体效价。小鼠没有产生针对干扰素-γ或IL-6的抗体。疫苗诱导的迟发型超敏反应可能会增强对艾滋病毒等病毒病原体的保护。含有细胞因子的脂质体可能是诱导包膜抗原亚单位疫苗产生迟发型超敏反应的有效佐剂。
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 vitrobioassays 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.