Ricin is on the list of toxic chemicals banned under the Chemical Weapons Convention^[1]: easily extracted from a widespread plant, the common castor bean, the protein is highly toxic to humans, and has already been the subject of attempted attacks. Although a vaccine to prevent ricin poisoning (RiVax™) is in clinical development, there is currently no commercially available prophylactic or therapeutic treatment for ricin poisoning to confer immediate protection in the event of poisoning.

Numerous studies have highlighted the potential of passive immunotherapy using anti-ricin monoclonal antibodies (mAbs) and have shown promising results in preclinical models. A team at LERI (SPI/DMTS) has developed a new generation of high-affinity anti-ricin monoclonal antibodies. A study published in the journal Toxins shows that :

• in vitro, these antibodies bind to the D and E isoforms of ricin and effectively neutralise them (cytotoxicity tests on cells);
• in vivo, one of these antibodies (RicE5) confers over 90% survival in a mouse model exposed intranasally to a dose equal to five times the 50% lethal dose (LD50) of ricin and treated by intravenous administration of RicE5 6 hours after exposure. The survival rate was still 35% when the antibody was administered late (24 hours) after intoxication. In addition, all the surviving mice developed a long-term immune response giving them protection against re-exposure to high doses of ricin more than 10 months after treatment.

These results are promising for the clinical development of a drug candidate against ricin poisoning and could also pave the way for new vaccination strategies against ricin or other toxins.

Contact Frédéric-Joliot Institute for Life Sciences:

Stéphanie Simon (stephanie.simon@cea.fr)

^[1] Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction​. | OPCW, 7 juin 2020