Moore A, McGuirk P, Adams S, Jones W C, McGee J P, O'Hagan D T, Mills K H
Biology Department, St. Patrick's College, Maynooth, Co. Kildare, Ireland.
Vaccine. 1995 Dec;13(18):1741-9. doi: 10.1016/0264-410x(95)00184-3.
One of the major obstacles to the development of successful recombinant vaccines against human immunodeficiency virus (HIV) and other intracellular pathogens is the identification of a safe and effective vaccine delivery system for the induction of cell mediated immunity with soluble protein antigens. In this study it was demonstrated that immunization with a recombinant HIV envelop (env) protein entrapped in biodegradable poly(lactide-co-glycolide) (PLG) microparticles induced consistent HIV-specific CD4+ and CD8+ T-cell responses in mice. Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) responses were detected following a single systemic immunization with gp120 entrapped microparticles and when given by the intranasal (i.n.) route induced HIV-specific CD8+ CTL and secretory IgA. Furthermore immunization with gp120 entrapped in microparticles generated CD4+ T cells that secreted moderate to high levels of IFN-gamma. Therefore, PLG microparticles are a safe and effective means of delivering antigen to the appropriate processing site for the generation of class I-restricted CTL, and are also capable of inducing Th1 cells.
开发成功的抗人类免疫缺陷病毒(HIV)及其他细胞内病原体的重组疫苗的主要障碍之一,是为用可溶性蛋白抗原诱导细胞介导免疫确定一种安全有效的疫苗递送系统。在本研究中,证明了用包裹于可生物降解的聚(丙交酯-共-乙交酯)(PLG)微粒中的重组HIV包膜(env)蛋白进行免疫,可在小鼠中诱导持续的HIV特异性CD4+和CD8+ T细胞应答。在用包裹有gp120的微粒进行单次全身免疫后,检测到主要组织相容性复合体(MHC)I类限制性细胞毒性T淋巴细胞(CTL)应答,且经鼻内(i.n.)途径给予时可诱导HIV特异性CD8+ CTL和分泌型IgA。此外,用包裹于微粒中的gp120进行免疫可产生分泌中到高水平干扰素-γ的CD4+ T细胞。因此,PLG微粒是一种将抗原递送至适当加工位点以产生I类限制性CTL的安全有效手段,并且还能够诱导Th1细胞。