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Hannelore Lotter^*, Tonghai Zhang, Karl B. Seydel, Samuel L. Stanley, Jr., and Egbert Tannich^*

From the ^* Department of Molecular Biology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; and the Department of Medicine and Molecular Microbiology, Washington University, School of Medicine, St. Louis, Missouri 63110

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.

The work was supported by the German Ministry for Education, Science, Research and Technology and in part by National Institutes of Health grant AI30084 and World Health Organization grant GPV-15181281 to S.L. Stanley, Jr. S.L. Stanley, Jr. is the recipient of Research Career Development Award AI-01231. K.B. Seydel is supported by National Institutes of Health grant 5T32AI-07172.

¹Abbreviations used in this paper: aa, amino acid; CHO, Chinese hamster ovary; RT, room temperature.

Dedicated to Dr. Hans J. Müller-Eberhard, Professor and Director, Institute of Molecular Medicine, The University of Texas-Houston, on the occasion of his seventieth birthday.

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