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

Exp Lung Res. Oct-Nov 2007;33(8-9):459-81. doi: 10.1080/01902140701731805.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies / therapeutic use*
  • Antibodies, Monoclonal / 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*

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Ricin