Alizadeh H, He Y, McCulley J P, Ma D, Stewart G L, Via M, Haehling E, Niederkorn J Y
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Cornea. 1995 Mar;14(2):180-6.
The feasibility of inducing protective immunity to Acanthamoeba keratitis was tested in a pig model. Experiments were designed to determine if ocular infection with Acanthamoeba trophozoites would elicit protection against reinfection. Additional experiments examined whether injection of parasite antigens either intramuscularly, subconjunctivally, or by both routes would induce immunity. Therefore, four groups of animals were examined: (a) pigs that had resolved a primary corneal infection with Acanthamoeba; (b) pigs immunized intramuscularly; (c) pigs immunized subconjunctivally; and (d) pigs immunized intramuscularly and subconjunctivally. Animals were subsequently challenged with parasite-laden soft contact lenses and observed clinically for the appearance of Acanthamoeba keratitis. Acanthamoeba-specific serum antibody titers and blastogenic responses of peripheral blood lymphocytes were determined weekly. The results indicated that intramuscular injection of Acanthamoeba antigens failed to protect against ocular infection even though hosts developed high titers of IgG antibodies and displayed lymphocyte blastogenic responses to parasite antigens. Ocular infection alone failed to stimulate immunity in any of the animals. By contrast, 50% of the hosts immunized subconjunctivally were protected against corneal disease, and 100% of the animals immunized by a combination of intramuscular and subconjunctival administration of parasite antigens were completely protected against two separate ocular challenges with infectious parasites. Protection did not correlate with either IgG antibody titers or blastogenic potentials of peripheral blood lymphocytes. Interestingly, ocular infection alone failed to stimulate immunity to subsequent ocular challenge with infectious parasites. Thus, administration of parasite antigen via the subconjunctival route can protect against Acanthamoeba keratitis.
在猪模型中测试了诱导针对棘阿米巴角膜炎的保护性免疫的可行性。设计实验以确定用棘阿米巴滋养体进行眼部感染是否会引发针对再次感染的保护作用。另外的实验研究了通过肌肉内、结膜下或两种途径注射寄生虫抗原是否会诱导免疫。因此,检查了四组动物:(a) 已解决原发性棘阿米巴角膜感染的猪;(b) 肌肉内免疫的猪;(c) 结膜下免疫的猪;以及 (d) 肌肉内和结膜下免疫的猪。随后用载有寄生虫的软性隐形眼镜对动物进行攻击,并临床观察棘阿米巴角膜炎的出现情况。每周测定棘阿米巴特异性血清抗体滴度和外周血淋巴细胞的增殖反应。结果表明,即使宿主产生了高滴度的IgG抗体并对外周血淋巴细胞的寄生虫抗原表现出增殖反应,肌肉内注射棘阿米巴抗原仍无法预防眼部感染。仅眼部感染未能在任何动物中刺激免疫。相比之下,50%的结膜下免疫宿主对角膜疾病有保护作用,并且100%通过肌肉内和结膜下联合给予寄生虫抗原免疫的动物对两次单独的感染性寄生虫眼部攻击完全有保护作用。保护作用与外周血淋巴细胞的IgG抗体滴度或增殖潜力均无关。有趣的是,仅眼部感染未能刺激对随后感染性寄生虫眼部攻击的免疫。因此,通过结膜下途径给予寄生虫抗原可预防棘阿米巴角膜炎。