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.
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.
Pratt
Timothy S
TS
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.
Pincus
Seth H
SH
Hale
Martha L
ML
Moreira
Andre L
AL
Roy
Chad J
CJ
Tchou-Wong
Kam-Meng
KM
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D008168:Lung / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009960:Oropharynx / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced; D012276:Ricin / Q000032:analysis / Q000276:immunology / Q000633:toxicity*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D012276:Ricin