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The Journal of Immunology, 2001, 166: 1855-1862.
Copyright © 2001 by The American Association of Immunologists

Outer Membrane Protein-Specific Monoclonal Antibodies Protect SCID Mice from Fatal Infection by the Obligate Intracellular Bacterial Pathogen Ehrlichia chaffeensis1

Julia Shu-yi Li*, Eric Yager*, Melissa Reilly{ddagger}, Christine Freeman{ddagger}, G. Roman Reddy{dagger}, Andrew A. Reilly{ddagger}, Frederick K. Chu{ddagger} and Gary M. Winslow2,*,{ddagger}

* Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, NY 12201; {dagger} Department of Diagnostic Medicine/Pathology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506; and {ddagger} Wadsworth Center, New York State Department of Health, Albany, NY 12201

Previous studies of Ehrlichia chaffeensis infection in the mouse have demonstrated that passive transfer of polyclonal Abs from resistant immunocompetent mice to susceptible SCID mice ameliorated infection and disease, even when Abs were administered during established infection. To identify particular Abs that could mediate bacterial clearance in vivo, E. chaffeensis-specific mAbs were generated and administered to infected SCID mice. Bacterial infection in the livers was significantly lowered after administration of either of two Abs of different isotypes (IgG2a and IgG3). Moreover, repeated administration of one Ab (Ec56.5; IgG2a) rescued mice from an otherwise lethal infection for at least 5 wk. Both protective Abs recognized the E. chaffeensis major outer membrane protein (OMP)-1g. Further studies revealed that both Abs recognized closely related epitopes within the amino terminus of the first hypervariable region of OMP-1g. Analyses of human sera showed that E. chaffeensis-infected patients also generated serological responses to OMP-1g hypervariable region 1, indicating that humans and mice recognize identical or closely related epitopes. These studies demonstrate that OMP-specific mAbs can mediate bacterial elimination in SCID mice, and indicate that Abs, in the absence of cell-mediated immunity, can play a significant role in host defense during infection by this obligate intracellular bacterium.




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