Ho R J, Burke R L, Merigan T C
Department of Medicine, Stanford University School of Medicine, CA 94305.
Antiviral Res. 1990 Apr;13(4):187-99. doi: 10.1016/0166-3542(90)90037-8.
Antigen presenting liposomes (APLs) containing both liposome encapsulated (44%) and free (56%) recombinant glycoprotein D of herpes simplex virus type-2 (rgD-2) were characterized with respect to the interaction of the antigen with the lipid bilayer and the biological activities provided by each form of rgD-2. We found that free rgD-2 added externally to empty liposomes exhibited some biological activities both in vitro and in vivo, although we could not detect any significant adsorption and/or insertion of this form of rgD-2 into the lipid bilayer. Compared to APLs containing both forms of rgD-2, purified liposomes containing only encapsulated rgD-2 gave only 50% of the relative activity in vitro as measured by their ability to stimulate rgD-2 specific lymphocyte proliferation, and 67% of the relative activity in vivo as measured by their immunotherapeutic effect on recurrent genital HSV-2 disease in guinea pigs (P less than 0.05). These data indicate that while liposome encapsulated rgD-2 is essential for the elicitation of immunogenic responses, the free soluble rgD-2 in the APL formulation also acts in concert to generate an optimum immunotherapeutic efficacy.
含有脂质体包裹型(44%)和游离型(56%)单纯疱疹病毒2型重组糖蛋白D(rgD-2)的抗原呈递脂质体(APL),就抗原与脂质双层的相互作用以及每种形式的rgD-2所提供的生物学活性进行了表征。我们发现,将游离的rgD-2外部添加到空脂质体中,在体外和体内均表现出一些生物学活性,尽管我们无法检测到这种形式的rgD-2在脂质双层中有任何明显的吸附和/或插入。与含有两种形式rgD-2的APL相比,仅含有包裹型rgD-2的纯化脂质体,通过刺激rgD-2特异性淋巴细胞增殖的能力来衡量,其体外相对活性仅为50%,通过对豚鼠复发性生殖器HSV-2疾病的免疫治疗效果来衡量,其体内相对活性为67%(P小于0.05)。这些数据表明,虽然脂质体包裹的rgD-2对于引发免疫原性反应至关重要,但APL制剂中的游离可溶性rgD-2也协同发挥作用,以产生最佳的免疫治疗效果。