Role of Fc in Antibody-Mediated Protection from Ricin Toxin |
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| Authors: | Seth. H. Pincus Anushka Das Kejing Song Grace A. Maresh Miriam Corti Jody Berry |
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| Affiliation: | 1.Children’s Hospital New Orleans, New Orleans, LA 70118, USA; E-Mails: (A.D.); (K.S.); (G.A.M.); (M.C.);2.Department of Pediatrics and Microbiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA;3.Tulane University, New Orleans, LA 70118, USA;4.Cangene Corporation (now Emergent Biosolutions Inc), Winnipeg, MB R3T 5Y3, Canada; E-Mail: |
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| Abstract: | We have studied the role of the antibody (Ab) Fc region in mediating protection from ricin toxicity. We compared the in vitro and in vivo effects of intact Ig and of Fab fragments derived from two different neutralizing Ab preparations, one monoclonal, the other polyclonal. Consistent results were obtained from each, showing little difference between Ig and Fab in terms of antigen binding and in vitro neutralization, but with relatively large differences in protection of animals. We also studied whether importing Ab into the cell by Fc receptors enhanced the intracellular neutralization of ricin toxin. We found that the imported Ab was found in the ER and Golgi, a compartment traversed by ricin, as it traffics through the cell, but intracellular Ab did not contribute to the neutralization of ricin. These results indicate that the Fc region of antibody is important for in vivo protection, although the mechanism of enhanced protection by intact Ig does not appear to operate at the single cell level. When using xenogeneic antibodies, the diminished immunogenicity of Fab/F(ab’)2 preparations should be balanced against possible loss of protective efficacy. |
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| Keywords: | ricin monoclonal antibody polyclonal antiserum Fc region Fc receptor Fab neutralization in vivo protection |
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