The emergence of multidrug-resistant organisms and the failure to eradicate
infection by a number of important pathogens has led to increased efforts to develop
vaccines to prevent
infectious 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
vaccine to prevent
amebiasis. Vaccination with the
lectin can induce protective immunity to
amebic liver abscess in some animals, but others of the same species exhibit exacerbations of disease after vaccination. To better understand this phenomenon, we used
recombinant proteins corresponding to four distinct domains of the molecule, and synthetic
peptides to localize both protective and exacerbative
epitopes of the heavy chain subunit of the
lectin. We show that protective immunity after vaccination can be correlated with the development of an antibody response to a region of 25
amino acid residues of the
lectin, and have confirmed the importance of the antibody response to this region by passive immunization studies. In addition, we show that exacerbation of disease 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 resistant to invasive disease have a high prevalence of
antibodies to the protective
epitope(s), compared to individuals with a history of invasive
amebiasis. These studies should enable us to develop an improved
vaccine for
amebiasis, and provide a model for the identification of protective and exacerbative
epitopes of complex
antigens.