Zaidi Tanweer, Pier Gerald B
Department of Medicine, Channing Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Infect Immun. 2008 Oct;76(10):4720-5. doi: 10.1128/IAI.00496-08. Epub 2008 Jul 21.
Treatment of ulcerative keratitis due to Pseudomonas aeruginosa is difficult, time-consuming, and uncomfortable owing to the need for the frequent application of antibiotic drops to the infected corneal surface. We examined here whether a fully human immunoglobulin G1 monoclonal antibody (MAb) specific to the conserved alginate surface polysaccharide of P. aeruginosa could mediate protective immunity against typically nonmucoid strains isolated from human cases of keratitis. MAb F429 effectively opsonized alginate-positive, but not alginate-negative, nonmucoid strains in conjunction with phagocytes and complement. Prophylactic administration of MAb F429 18 h prior to infection with two clinical isolates significantly reduced bacterial levels in the eye and the associated corneal pathology. Along similar lines, systemic intraperitoneal injection, as well as topical application of the MAb onto the infected eye, starting 8 h postinfection in both experimental protocols resulted in significant reductions in bacteria in the eye, as well as minimizing pathological damage to the cornea. These findings indicate that MAb F429 could be useful as an additional therapeutic component for the treatment of P. aeruginosa keratitis.
由于需要频繁地向受感染的角膜表面滴注抗生素,铜绿假单胞菌所致溃疡性角膜炎的治疗既困难、耗时又令人不适。我们在此研究了一种针对铜绿假单胞菌保守藻酸盐表面多糖的全人源免疫球蛋白G1单克隆抗体(MAb)是否能介导针对从人类角膜炎病例中分离出的典型非黏液型菌株的保护性免疫。MAb F429能与吞噬细胞和补体协同有效地调理藻酸盐阳性而非藻酸盐阴性的非黏液型菌株。在感染两种临床分离株前18小时预防性给予MAb F429可显著降低眼中细菌水平及相关的角膜病变。同样,在两个实验方案中,感染后8小时开始全身腹腔注射以及将MAb局部应用于感染眼,均能显著减少眼中细菌数量,并将角膜的病理损伤降至最低。这些发现表明,MAb F429可作为治疗铜绿假单胞菌角膜炎的一种额外治疗成分。