Following inhalation, ricin toxin, a plant-derived, mannosylated glycoprotein, causes an incapacitating and potentially fatal inflammatory reaction in the airways. Ricin is taken up by alveolar macrophages (AM) and other pulmonary cell types by two parallel pathways: one mediated by ricin’s B component (RTB), a galactose-specific lectin, and the other by the mannose receptor. A single monoclonal antibody, PB10, designed against an immunodominant epitope on RTA and given intravenously, was recently shown to be capable of rescuing Rhesus macaques from a fatal aerosol dosage of ricin.

In this work, researchers show that when PB10 is coupled with a second MAb, SylH3, its efficacy against RTB is considerably enhanced in mice. Mice treated with PB10 alone survived a lethal-dose intranasal ricin challenge, but had substantial weight loss, mild pulmonary inflammation, and lung macrophage death. Mice treated with the PB10/SylH3 cocktail, on the other hand, were essentially immune to pulmonary ricin toxin exposure, as evidenced by no weight loss, no change in local IL-1 and IL-6 levels, lung macrophage retention, and a significant dampening of PMN recruitment into bronchoalveolar lavage (BAL) fluids. The PB10/SylH3 cocktail only minimally decreased ricin binding to target cells in the BAL, indicating that the antibody combination neutralises ricin by interfering with one or more stages in the RTB- and MR-dependent absorption pathways.