THE DEVELOPMENT OF PROTECTIVE MONOCLONAL ANTIBODIES AGAINST TETRODOTOXIN

THE OVERALL GOAL OF THIS SBIR PROPOSAL IS THE DEVELOPMENT OF HUMAN MONOCLONAL ANTIBODIES (MABS) THAT BIND TO AND NEUTRALIZE TETRODOTOXIN (TTX), A LOW MOLECULAR WEIGHT NEUROTOXIN. IN PHASE I WE WILL PREPARE A SERIES OF TTX CONJUGATE VACCINES TO PREPARE MURINE MABS THAT BIND TO VARIOUS REGIONS OF THE TOXIN MOLECULE. WE THUS HOPE TO IDENTIFY IMMUNOGENS SUITABLE FOR USE IN PREPARING HUMAN MONOCLONALS AGAINST TTX IN PHASE II. NEUTRALIZING HUMAN MABS ARE EXPECTED TO BE USEFUL FOR BOTH THE PROPHYLAXIS AND THERAPY OF TETRODOTOXIN POISONING AND COULD BE IMPORTANT IN THE DEVELOPMENT OF POTENTIALLY PROTECTIVE ANALOGS. MABS PRODUCED IN PHASE I MAY ALSO BE USEFUL FOR THE DEVELOPMENT OF RAPID AND SENSITIVE ASSAYS FOR THE DETECTION OF TTX HAVING COMMERCIAL AND DEFENSE APPLICATIONS. MORE IMPORTANTLY, THESE STUDIES SHOULD ALSO LEAD TO IMPROVE METHODS OF PRODUCING HUMAN MABS AGAINST OTHER NONIMMUNOGENIC COMPOUNDS AND THUS COULD BE BROADLY APPLICABLE TO THE DEVELOPMENT OF REAGENTS AND THERAPEUTICS FOR OTHER TOXINS AND LOW MOLECULAR WEIGHT DRUGS HAVING NARROW THERAPEUTIC INDICES.