Title: Oropharyngeal aspiration of ricin as a lung challenge model for evaluation of the therapeutic index of antibodies against ricin A-chain for post-exposure treatment.
Authors: Pratt, Timothy S; Pincus, Seth H; Hale, Martha L; Moreira, Andre L; Roy, Chad J; Tchou-Wong, Kam-Meng
Published In Exp Lung Res, (2007 Oct-Nov)
Abstract: To investigate the effectiveness of passive antibody treatment as post-exposure therapy for ricin, we had developed an oropharyngeal aspiration model for ricin lethal challenge and antibody administration. When polyclonal anti-deglycosylated ricin A-chain antibody (dgA Ab) was administered between 1-18 hr after ricin challenge, all animals survived while delayed treatment to 24 hr resulted in 30% survival. The protective effects of dgA Ab correlated with inhibition of apoptosis in the lungs in vivo and in RAW264.7 macrophage and Jurkat T cells in vitro. In addition, ricin-induced cell cytotoxicity was inhibited by both dgA Ab and RAC18 monoclonal antibody against ricin A-chain. Administration of RAC18 monoclonal antibody at 4, 18, and 24 hr after ricin exposure resulted in 100%, 60% and 50% protection, respectively, suggesting that the therapeutic window for passive vaccination extended to at least 24 hr post-ricin lung challenge.
PubMed ID: 17994372
MeSH Terms: Animals; Antibodies, Monoclonal/therapeutic use; Antibodies/therapeutic use*; Apoptosis/drug effects; Cell Line; Cell Survival/drug effects; Humans; Inflammation/chemically induced; Lung/drug effects*; Male; Mice; Mice, Inbred BALB C; Oropharynx/drug effects; Pulmonary Edema/chemically induced; Ricin/analysis; Ricin/immunology; Ricin/toxicity*