A Monoclonal Antibody with a High Affinity for Ricin Isoforms D and E Provides Strong Protection against Ricin...

Area of Science:

• Toxicology
• Immunology
• Biodefense

Background:

• Ricin is a potent bioterrorism toxin with no current treatments.
• Existing vaccine development (RiVax™) is ongoing, but therapeutic options are lacking.
• Passive immunotherapy with monoclonal antibodies (mAbs) shows preclinical promise.

Purpose of the Study:

• To evaluate the neutralizing and protective efficacy of novel high-affinity anti-ricin mAbs.
• To assess the therapeutic potential of these mAbs against ricin intoxication in vivo.

Main Methods:

• In vitro cytotoxicity cell assays to assess neutralization of ricin isoforms D and E.
• In vivo protection assays using a murine model challenged intranasally with ricin.
• Intravenous administration of anti-ricin mAbs at different time points post-intoxication.

Main Results:

• Novel mAbs efficiently neutralized ricin isoforms D and E in vitro.
• One mAb (RicE5) conferred >90% survival in mice treated 6 hours post-intoxication.
• Significant survival (35%) was observed even with treatment 24 hours post-exposure.
• Surviving mice developed long-term immunity to ricin.

Conclusions:

• High-affinity anti-ricin mAbs demonstrate potent neutralizing and protective capabilities.
• RicE5 is a promising therapeutic candidate for clinical development against ricin intoxication.
• These findings may inform novel vaccination strategies against ricin and other toxins.