PRODUCTION AND CHARACTERIZATION OF AN AVIAN RICIN ANTITOXIN

OPHIDIAN PHARMACEUTICALS PROPOSES TO TEST THE FEASIBILITY OF ADAPTING ITS TECHNOLOGY FOR PRODUCING AND PURIFYING THERAPEUTIC ANTIBODIES FROM THE EGG YOLKS OF HYPERIMMUNIZED LAYING HENS TO THE DEVELOPMENT OF RICIN ANTITOXIN. THIS TECHNOLOGY IS WELL SUITED TO THE RAPID DEVELOPMENT OF TOXIN-NEUTRALIZING THERAPEUTICS AGAINST HIGHLY-VARIABLE TOXINS OR A WIDE VARIETY OF TOXIC THREATS. COMMERCIALLY AVAILABLE ANTITOXINS ARE TYPICALLY PARTIALLY FRACTIONATED SERUM ANTIBODIES DERIVED FROM HORSES HYPERIMMUNIZED WITH TOXIN OR TOXOID (HOWEVER NO COMMERCIAL RICIN ANTITOXIN EXISTS). THESE ANTIBODY PREPARATIONS, WHILE EFFECTIVE IN MITIGATING THE TOXIC EFTECTS OF THE POISON, OFTEN ELICIT SERIOUS AND SOMETIMES LIFE THREATENING SIDE EFFECTS. HORSE-DERIVED ANTI-BODIES CAN INDUCE ANTI-COMPLEMENT ACTIVITY AND ANAPHYLAXIS, AND IF LARGE AMOUNTS OF ANTITOXIN ARE REQUIRED, SERUM SICKNESS IS FREQUENTLY OBSERVED. THE AVIAN PRODUCTION SYSTEM HAS BEEN USED TO DEVELOP EFFECTIVE ANTIDOTES AGAINST COMPLEX ANIMAL VENOMS, AND ARE EXPECTED TO SIGNIFICANTLY REDUCE OR ELIMINATE THOSE SIDE EFFECTS ASSOCIATED WITH HORSE (OR MAMMALIAN)-DERIVED IMMUNOTHERAPIES. FURTHERMORE, THE AVIAN MANUFACTURING PROCESS MAKES PRACTICAL THE RAPID DEVELOPBENT AND LARGE SCALE PRODUCTIOIN OF ANTITOXINS AGAINST RICIN AND OTHER TOXINS OF MILITARY CONCERN. THE PROPOSED RESEARCH WILL INCLUDE THE DEVELOPMENT OF A HIGHLY PURIFIED AVIAI RICIN ANTITOXIN AND CHARACTERIZATION OF ITS TOXIN NEUTRALIZATION CAPABILITIES IN LABORATORY ANIMALS.