Alving C R, Richards R L
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Immunol Lett. 1990 Aug;25(1-3):275-9. doi: 10.1016/0165-2478(90)90127-c.
Liposomes containing lipid A have been developed as adjuvants for inducing humoral immunity to synthetic antigens containing repeat sequence epitopes from the circumsporozoite protein of Plasmodium falciparum. Preclinical studies demonstrated that liposomes containing lipid A and encapsulated antigen could overcome immunosuppression observed with antigen alone. When liposomes containing lipid A were adsorbed with aluminum hydroxide (alum), further stimulation of humoral immunity against encapsulated antigen was observed in animals. In the presence of huge doses of liposomal lipid A pyrogenicity was not observed and adjuvant activity was enhanced. A phase I human clinical trial has been initiated utilizing a vaccine containing a synthetic recombinant antigen and monophosphoryl lipid A in liposomes and nonliposomal alum as a further adjuvant. Preliminary results confirm that the vaccine lacks significant acute toxicity in humans and causes very strong specific humoral immunity against the appropriate epitopes of the target antigen.
含有脂多糖A的脂质体已被开发用作佐剂，以诱导对含有来自恶性疟原虫环子孢子蛋白重复序列表位的合成抗原产生体液免疫。临床前研究表明，含有脂多糖A和包裹抗原的脂质体能够克服单独使用抗原时观察到的免疫抑制。当含有脂多糖A的脂质体与氢氧化铝（明矾）吸附时，在动物中观察到对包裹抗原的体液免疫进一步受到刺激。在存在大量脂质体脂多糖A的情况下，未观察到热原性，且佐剂活性增强。一项I期人体临床试验已启动，该试验使用一种疫苗，该疫苗含有脂质体中的合成重组抗原和单磷酰脂质A以及非脂质体明矾作为进一步的佐剂。初步结果证实，该疫苗在人体中缺乏明显的急性毒性，并能针对靶抗原的适当表位产生非常强烈的特异性体液免疫。
