Durable Immunity to Ricin Toxin Elicited by Intranasally Administered Monoclonal Antibody-Based Immune Complexes

Area of Science:

• Immunology
• Toxicology
• Respiratory Medicine

Background:

• Ricin toxin (RT) inhalation causes severe lung inflammation and acute respiratory distress syndrome.
• Previous studies showed intranasal antibody mixtures neutralize pulmonary RT effects.

Purpose of the Study:

• To evaluate the efficacy of an RT-mAb immune complex (RIC) in inducing protective immunity against ricin toxin.
• To determine the durability and mechanism of RIC-induced immunity.

Main Methods:

• Mice were administered RIC intranasally or intraperitoneally.
• Serum IgG and toxin-neutralizing antibody titers were measured.
• Mice were challenged with RT to assess immunity at 30 and 90 days.
• FcγR knockout mice and LALA mutant antibodies were used to investigate FcγR engagement.

Main Results:

• Intranasal or i.p. RIC administration induced persistent, high-titer RT-specific serum IgG and neutralizing antibodies.
• RIC treatment conferred immunity to a subsequent RT challenge.
• Intranasal RIC delivery was superior to i.p. for protection against inhaled RT.
• Immune response to RIC was independent of FcγR engagement.

Conclusions:

• A single intranasal RIC dose establishes durable protective immunity to ricin toxin in mice.
• The FcγR-independent pathway is crucial for RIC-mediated immunity.
• RIC represents a promising strategy for ricin antitoxin development.