Monoclonal IgA antibodies protect against Acanthamoeba keratitis

Acanthamoeba keratitis is a rare, yet sight-threatening corneal infection. Ocular infection does not appear to induce protective immunity as repeated corneal infections occur in both humans and experimental animals. However, we have recently demonstrated that activation of the common mucosal immune system by oral immunization with Acanthamoeba antigens protects both Chines e hamsters and pigs against ocular infection with A. castellanii. Protectio n correlates closely with the appearance of anti-Acanthamoeba antibodies in the tears. To test the hypothesis that oral immunization induces specific protective IgA antibodies, two monoclonal IgA antibodies specific for Acant hamoeba antigens were generated. Both antibodies detected epitopes on the s urface of fixed Acanthamoeba trophozoites. When delivered intraperitoneally , one monoclonal antibody (14E4) was detected in stool and tear samples. Th is clone also protected naive animals against ocular challenge with Acantha moeba trophozoites (43% infection rate compared to a 91% infection rate in animals receiving control IgA). In vitro functional studies showed that nei ther antibody induced encystment or directly killed Acanthamoeba trophozoit es. However, both monoclonal anti-Acanthamoeba IgA antibodies produced a th ree-fold inhibition in the adherence of trophozoites to corneal epithelial cells in vitro. These data show that monoclonal anti-Acanthamoeba IgA antib odies can protect against Acanthamoeba keratitis and suggest that this occu rs by inhibiting adhesion of the parasite to the corneal epithelium. (C) 19 99 Academic Press.