Alving Carl R, Rao Mangala
Department of Adjuvant and Antigen Research, U.S. Military HIV Vaccine Research Program, Walter Reed Army Institute of Research, Rockville, MD 20350, USA.
Vaccine. 2008 Jun 6;26(24):3036-45. doi: 10.1016/j.vaccine.2007.12.002. Epub 2007 Dec 26.
Lipid A derived from Gram-negative bacterial lipopolysaccharide is a potent adjuvant and antigen. Incorporation of lipid A into liposomes renders the liposomes themselves immunogenic, resulting in generation of specific antibodies that recognize either the individual liposomal lipids, or the unique pattern presented by the combination of lipids. Using liposomes containing lipid A, numerous polyclonal antisera and monoclonal antibodies have been produced against phospholipids, cholesterol, glycosphingolipids, and lipid A. Many of these antibodies have binding characteristics that are apparently similar to natural antibodies that are normally present in all human sera, and also antibodies that arise in response to various infections. Such antibodies probably represent a bridge between innate and adaptive immunity. The possible utility of liposomes containing lipid A as a constituent of certain types of novel vaccines was suggested by the observation that murine monoclonal antibodies to liposomal phosphatidylinositol-4-phosphate neutralized primary isolates of two different clades of HIV-1 in a human peripheral blood mononuclear cell neutralization assay.
源自革兰氏阴性菌脂多糖的脂质A是一种有效的佐剂和抗原。将脂质A掺入脂质体可使脂质体本身具有免疫原性,从而产生识别单个脂质体脂质或脂质组合呈现的独特模式的特异性抗体。使用含有脂质A的脂质体,已产生了许多针对磷脂、胆固醇、糖鞘脂和脂质A的多克隆抗血清和单克隆抗体。这些抗体中的许多具有与所有人类血清中通常存在的天然抗体以及对各种感染产生的抗体明显相似的结合特性。此类抗体可能代表了先天免疫和适应性免疫之间的桥梁。在人类外周血单核细胞中和试验中,针对脂质体磷脂酰肌醇-4-磷酸的鼠单克隆抗体可中和两种不同HIV-1进化枝的原始分离株,这一观察结果提示了含有脂质A的脂质体作为某些新型疫苗成分的潜在用途。