Passive transfer of a monoclonal antibody specific for a sialic acid-dependent epitope on the surface of Trypanosoma cruzi trypomastigotes reduces infection in mice

Abstract

Trypanosoma cruzi, the parasite that causes Chagas' disease, proliferates in the cytosol of mammalian cells. When the trypomastigote forms exit the infected cell, they become extensively sialylated because the parasite contains an enzyme called trans-sialidase. This enzyme efficiently catalyzes the transfer of bound sialic acid residues from host glycoconjugates to acceptors containing terminal ␤-galactosyl residues on the parasite surface. The sialic acid acceptors are developmentally regulated mucin-like glycoproteins that are extremely abundant on the trypomastigote surface. In the present study, we determined whether passive transfer of monoclonal antibodies specific for sialic acid acceptors could reduce the acute infection induced by T. cruzi in a highly susceptible mouse strain. We found that passive transfer to naive mice of an immunoglobulin G1 monoclonal antibody directed to a sialylated epitope of these mucin-like glycoproteins significantly decreased parasitemia and the number of tissue parasites as measured by a DNA probe specific for T. cruzi. Upon challenge with trypomastigotes, mice which received this antibody also had a significant increase in survival. A statistically significant reduction in parasitemia could be accomplished with relatively small doses of immunoglobulin, and Fab fragments 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 complement or mouse spleen cells.

Comparison of antibody and protective immune responses against Trypanosoma cruzi infection elicited by immunization with a parasite antigen delivered as naked DNA or recombinant protein

“…In addition to T cells, immunity to T. cruzi during experimental infection can be also mediated by antibodies to surface antigens of trypomastigotes (Krettli & Brenner 1976, Umekita et al 1988, Franchin et al 1997. As mentioned in our earlier study (Costa et al 1998), it is plausible that antibodies that inhibit TS enzymatic activity participate in protective immunity.…”

Reaching for the Holy Grail: insights from infection/cure models on the prospects for vaccines for Trypanosoma cruzi infection

“…With respect to the preventing host cell entry, the passive transfer of high-titre antibodies can reduce parasite loads ( Franchin et al 1997 ), presumably through the ability to target extracellular trypomastigotes for destruction by complement or phagocytic cells, or to block the ability of these parasites to invade host cells. However this approach has not been demonstrated to actually prevent infection and the antibodies produced during the course of acute and chronic infections, although contributing to immune control of the infection ( Kumar & Tarleton 1998 ) clearly lack the ability to prevent the constant reinfection of host cells that maintains the infection.…”

The Trypanosoma cruzi trans-Sialidase, through Its Cooh-Terminal Tandem Repeat, Upregulates Interleukin 6 Secretion in Normal Human Intestinal Microvascular Endothelial Cells and Peripheral Blood Mononuclear Cells

“…cruzi invasion, as suggested by the enhancement of infection in experimental models of Chagas's disease by LTR-specific polyclonal 61 and monoclonal 6224 antibodies, and by the inhibition of infection by CD-specific antibodies 6364. In addition, antibodies against TS-generated sialyl epitopes present on the trypomastigote surface block infection as well 65. Finally, the enhancement of T .…”