Defoort J P, Nardelli B, Huang W, Ho D D, Tam J P
Rockefeller University, New York, NY 10021.
Proc Natl Acad Sci U S A. 1992 May 1;89(9):3879-83. doi: 10.1073/pnas.89.9.3879.
We describe a peptide vaccine model based on the mimicry of surface coat protein of a pathogen. This model used a macromolecular assemblage approach to amplify peptide antigens in liposomes or micelles. The key components of the model consisted of an oligomeric lysine scaffolding to amplify peptide antigens covalently 4-fold and a lipophilic membrane-anchoring group to further amplify noncovalently the antigens many-fold in liposomal or micellar form. A peptide antigen derived from the third variable domain of glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1), consisting of neutralizing, T-helper, and T-cytotoxic epitopes, was used in a macromolecular assemblage model (HIV-1 linear peptide amino acid sequence 308-331 in a tetravalent multiple antigen peptide system linked to tripalmitoyl-S-glycerylcysteine). The latter complex, in liposome or micelle, was used to immunize mice and guinea pigs without any adjuvant and found to induce gp120-specific antibodies that neutralize virus infectivity in vitro, elicit cytokine production, and prime CD8+ cytotoxic T lymphocytes in vivo. Our results show that the macromolecular assemblage approach bears immunological mimicry of the gp120 of HIV virus and may lead to useful vaccines against HIV infection.
我们描述了一种基于病原体表面包膜蛋白模拟的肽疫苗模型。该模型采用大分子组装方法在脂质体或胶束中扩增肽抗原。该模型的关键组成部分包括一个寡聚赖氨酸支架，用于将肽抗原共价扩增4倍，以及一个亲脂性膜锚定基团，用于以脂质体或胶束形式将抗原非共价进一步扩增许多倍。一种源自人类免疫缺陷病毒1型（HIV-1）糖蛋白gp120第三个可变结构域的肽抗原，由中和、T辅助和T细胞毒性表位组成，被用于大分子组装模型（在与三棕榈酰-S-甘油半胱氨酸连接的四价多抗原肽系统中的HIV-1线性肽氨基酸序列308-331）。后者在脂质体或胶束中的复合物，用于在无任何佐剂的情况下免疫小鼠和豚鼠，发现可诱导gp120特异性抗体，这些抗体在体外中和病毒感染性，引发细胞因子产生，并在体内激发CD8+细胞毒性T淋巴细胞。我们的结果表明，大分子组装方法具有HIV病毒gp120的免疫模拟作用，可能会产生针对HIV感染的有效疫苗。
