Zeitschrift für Bioterrorismus und Bioverteidigung

Abstrakt

Development of Anti-Toxins Antibodies for Biodefense

Thibaut Pelat, Arnaud Avril, Siham Chahboun, Jacques Mathieu and Philippe Thullier

Antibodies (Abs) may significantly improve the outcome of diseases caused by toxins of military interest, in particular ricin and botulism toxins. The efficacy of Abs to neutralize ricin was demonstrated in vivo utilizing Abs of animal origin but recombinant antibodies (rAbs), which would be better tolerated, are preferred for clinical use. Animal Abs are utilized at present as medical countermeasure to neutralize botulism toxins, but they show limitations and rAbs are also preferred for this clinical use. Of note, anthrax is an infective disease depending on toxins for its pathogenicity, and it was demonstrated that anti-anthrax toxins Abs could be of benefit when used as adjunct to antibiotics. We used an original strategy, starting from libraries derived from lymphocytes of non-human primates (NHP) immunized with the toxin of interest, to isolate Abs directed against all these toxins. The libraries are screened by the phage-display technology to isolate the best candidates, which are then tested for their toxin neutralization properties. Abs neutralizing the anthrax lethal toxin (35PA83, 2LF) and ricin (43RCA) have been isolated and at present, Abs neutralizing the botulinum toxins (BoNT) A, B and E are being isolated.