IDENTIFICATION OF AN EPITOPE ON THE ENTAMOEBA-HISTOLYTICA 170-KD LECTIN CONFERRING ANTIBODY-MEDIATED PROTECTION AGAINST INVASIVE AMEBIASIS

The emergence of multidrug-resistant organisms and the failure to erad icate infection by a number of important pathogens has led to increase d efforts to develop vaccines to prevent injections diseases. However, the nature of the immune response to vaccination with a given antigen can be complex and unpredictable. An example is the galactose- and N- acetylgalactosamine-inhibitable lectin, a surface antigen of Entamoeba histolytica that has been identified as a major candidate in a vaccin e to prevent amebiasis. Vaccination with the lectin can induce protect ive immunity to amebic liver abscess in some animals, but others of th e same species exhibit exacerbations of disease after vaccination. To better understand this phenomenon, we used recombinant proteins corres ponding to four distinct domains of the molecule, and synthetic peptid es to localize both protective and exacerbative epitopes of the heavy chain subunit of the lectin. We show that protective immunity after va ccination can be correlated with the development of an antibody respon se to a region of 25 amino acid residues of the lectin, and have confi rmed the importance of the antibody response to this region by passive immunization studies. In addition, we show that exacerbation of disea se can be linked to the development of antibodies that bind to an NH2- terminal domain of the lectin. These findings are clinically relevant, as individuals who are colonized with E. histolytica but are resistan t to invasive disease have a high prevalence of antibodies to the prot ective epitope(s), compared to individuals with a history of invasive amebiasis. These studies should enable us to develop an improved vacci ne for amebiasis, and provide a model for the identification of protec tive and exacerbative epitopes of complex antigens.