Kuo P Y, Sherwood J K, Saltzman W M
School of Chemical Engineering, Cornell University, Ithaca, NY 14853, USA.
Nat Biotechnol. 1998 Feb;16(2):163-7. doi: 10.1038/nbt0298-163.
Immunity at mucosal surfaces, which are ports of entry for many pathogens, is essential in preventing infections. But most current strategies for passive immunization involve injection of antibodies for systemic, not mucosal, protection. We measured mucosal and systemic antibody levels after controlled topical delivery to the vagina. Poly(ethylene-co-vinyl acetate) disks containing 125I-labeled monoclonal IgG or anti-lactate dehydrogenase-C4 antibodies were placed in the vaginas of mice. High antibody levels (0.26-12 micrograms/ml) were maintained at the mucosal surface for 7 days after disk insertion. Antibody molecules also penetrated into the vaginal epithelium, presumably by diffusing through the extracellular space, and entered the circulation. Biologically active antibodies were detected in the blood. The antibody concentration in the blood was approximately 1% of the concentration in the vagina. Although the permeability of the epithelium to macro-molecules is low, high concentrations were maintained at the luminal surface for an extended period, permitting substantial systemic uptake of antibody.
粘膜表面是许多病原体的入侵门户,其免疫对于预防感染至关重要。但目前大多数被动免疫策略涉及注射抗体以提供全身而非粘膜保护。我们在向阴道进行可控局部递送后测量了粘膜和全身抗体水平。将含有125I标记的单克隆IgG或抗乳酸脱氢酶-C4抗体的聚(乙烯-共-醋酸乙烯酯)圆盘置于小鼠阴道内。圆盘插入后7天,粘膜表面维持着高抗体水平(0.26 - 12微克/毫升)。抗体分子大概通过细胞外间隙扩散进入阴道上皮,并进入循环系统。在血液中检测到了具有生物活性的抗体。血液中的抗体浓度约为阴道内浓度的1%。尽管上皮对大分子的通透性较低,但在管腔表面长时间维持了高浓度,从而允许抗体大量被全身吸收。