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 Chinese hamsters and pigs against ocular infection with A. castellanii. Protection 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 Acanthamoeba antigens were generated. Both antibodies detected epitopes on the surface of fixed Acanthamoeba trophozoites. When delivered intraperitoneally, one monoclonal antibody (14E4) was detected in stool and tear samples. This clone also protected naive animals against ocular challenge with Acanthamoeba trophozoites (43% infection rate compared to a 91% infection rate in animals receiving control IgA). In vitro functional studies showed that neither antibody induced encystment or directly killed Acanthamoeba trophozoites. However, both monoclonal anti- Acanthamoeba IgA antibodies produced a three-fold inhibition in the adherence of trophozoites to corneal epithelial cells in vitro. These data show that monoclonal anti- Acanthamoeba IgA antibodies can protect against Acanthamoeba keratitis and suggest that this occurs by inhibiting adhesion of the parasite to the corneal epithelium.
Leher
H
H
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, 75235-9057, USA.
Zaragoza
F
F
Taherzadeh
S
S
Alizadeh
H
H
Niederkorn
J Y
JY
D000048:Acanthamoeba / Q000276:immunology*; D015823:Acanthamoeba Keratitis / Q000517:prevention & control*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000913:Antibodies, Protozoan / Q000627:therapeutic use*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D019573:Epithelium, Corneal / Q000469:parasitology; D007116:Immunization, Passive; D007070:Immunoglobulin A / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D007070:Immunoglobulin A