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Toxins 2014, 6(5), 1512-1525;

Role of Fc in Antibody-Mediated Protection from Ricin Toxin

Children's Hospital New Orleans, New Orleans, LA 70118, USA
Department of Pediatrics and Microbiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Tulane University, New Orleans, LA 70118, USA
Cangene Corporation (now Emergent Biosolutions Inc), Winnipeg, MB R3T 5Y3, Canada
Current addresses: Department of Physiology, LSU Health Sciences Center, New Orleans, LA 70118, USA
Current addresses: BD Biosciences, San Diego, CA 92121, USA
Author to whom correspondence should be addressed.
Received: 4 February 2014 / Revised: 24 March 2014 / Accepted: 28 March 2014 / Published: 7 May 2014
(This article belongs to the Special Issue Toxin-Antibody Interactions)
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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. View Full-Text
Keywords: ricin; monoclonal antibody; polyclonal antiserum; Fc region; Fc receptor; Fab; neutralization; in vivo protection ricin; monoclonal antibody; polyclonal antiserum; Fc region; Fc receptor; Fab; neutralization; in vivo protection

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Pincus, S.H.; Das, A.; Song, K.; Maresh, G.A.; Corti, M.; Berry, J. Role of Fc in Antibody-Mediated Protection from Ricin Toxin. Toxins 2014, 6, 1512-1525.

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