An Effective Prophylactic and Therapeutic Protection Against Botulinum Type A Intoxication in Mice and Rabbits Using...

Area of Science:

• Immunology
• Toxicology
• Pharmacology

Background:

• Botulinum neurotoxins (BoNTs) are highly potent toxins causing paralysis and are classified as Category A agents.
• Antibody therapeutics are effective treatments for toxin-mediated diseases.
• Botulism remains a significant health concern requiring effective countermeasures.

Purpose of the Study:

• To develop and evaluate a humanized monoclonal antibody (HZ45 mAb) for preventing and treating botulism.
• To assess the efficacy of HZ45 mAb against botulinum neurotoxin serotype A (BoNT/A).

Main Methods:

• Generation of HZ45 mAb using hybridoma technology and phage display.
• Evaluation of HZ45 mAb neutralization of BoNT/A in vivo models (mice and rabbits).
• Assessment of protective and therapeutic efficacy based on survival rates and treatment timelines.

Main Results:

• HZ45 mAb provided 100% protection in mice at a dose of 0.1 mg/mouse against 100 LD50 of BoNT/A.
• In rabbits, a 5 mg dose of HZ45 mAb demonstrated therapeutic efficacy when administered up to 8 hours post-exposure to 10 LD50 of BoNT/A.
• HZ45 mAb successfully prevented botulism intoxication in both mice and rabbits.

Conclusions:

• Humanized monoclonal antibody HZ45 mAb is a promising candidate for preventing and treating botulinum type A intoxication.
• HZ45 mAb neutralizes BoNT/A by binding to its heavy chain receptor domain, blocking cellular entry.
• The study validates HZ45 mAb's efficacy in preclinical models, supporting its potential as a pharmaceutical intervention.