PASSIVE TRANSFER OF A MONOCLONAL-ANTIBODY SPECIFIC FOR A SIALIC ACID-DEPENDENT EPITOPE ON THE SURFACE OF TRYPANOSOMA-CRUZI TRYPOMASTIGOTES REDUCES INFECTION IN MICE

Trypanosoma cruzi, the parasite that causes Chagas' disease, prolifera tes in the cytosol of mammalian cells. When the trypomastigote forms e xit the infected cell, they become extensively sialylated because the parasite contains an enzyme called trans-sialidase. This enzyme effici ently catalyzes the transfer of bound sialic acid residues from host g lycoconjugates to acceptors containing terminal beta-galactosyl residu es on the parasite surface, The sialic acid accepters are developmenta lly regulated mucin-like glycoproteins that are extremely abundant on the trypomastigote surface. In the present study, we determined whethe r passive transfer of monoclonal antibodies specific for sialic acid a cceptors could reduce the acute infection induced by T. cruzi in a hig hly susceptible mouse strain. We found that passive transfer to naive mice of an immunoglobulin G1 monoclonal antibody directed to a sialyla ted epitope of these mucin-like glycoproteins significantly decreased parasitemia and the number of tissue parasites as measured by a DNA pr obe specific for T. cruzi. Upon challenge with trypomastigotes, mice w hich received this antibody also had a significant increase in surviva l. A statistically significant reduction in parasitemia could be accom plished with relatively small doses of immunoglobulin, and Fab fragmen ts alone could not mediate protective immunity. The precise mechanism of parasite elimination is unknown; however; this monoclonal antibody does not lyse trypomastigotes in vitro in the presence of human comple ment or mouse spleen cells.