Applicants:

Dr. Karin Weisser

Paul Ehrlich-Institute (Federal Institute for Vaccines and Biomedicines)

63225 Langen, Germany

Telefon: +49 6103 77 1024 

E-Mail: Karin.Weisser@pei.de

Dr. Beate Krämer 

Paul Ehrlich-Institute (Federal Institute for Vaccines and Biomedicines)

63225 Langen, Germany

Telefon: +49 6103 77 7412 

E-Mail: Beate.Kraemer@pei.de

Problems and aims:

Tetanus vaccines are produces by treating tetanus neurotoxin (TeNT) with formalin. As a result of the formalin treatment a toxoid is produced which is still immunogenic but not toxic. In order to exclude any toxic potential of a tetanus toxoid it must be tested for “Absence of toxin and irreversibility of toxoid”. This test is mandatory according to the European Pharmacopoeia and is performed on animal models. For that purpose the toxoid is injected into guinea pigs or mice which are later examined for any symptoms of tetanus. For every toxoid batch at least 15 animals are used. Based on the annual batch release at the Paul-Ehlich Institute it is estimated that the use of animals for tetanus toxoid testing reaches approximately 3000 animals per year at this institution only. In all Europe this number is certainly much higher.

Our aim is to develop an in vitro method for the determination of tetanus toxicity which can replace animal models used for this purpose. The inclusion of such a method in the European Pharmacopoeia would have an impact throughout Europe.

Outcomes:

Behrensdorf-Nicol HA, Bonifas U, Kegel B, Silberbach K, Krämer B, Weisser K (2010). In vitro determination of tetanus toxicity by an endopeptidase assay linked to a ganglioside-binding step. Toxicol In Vitro 24(3):988-94.

Behrensdorf-Nicol HA, Weisser K, Krämer B (2015). “BINACLE” assay for in vitro detection of active tetanus neurotoxin in toxoids. ALTEX 32(2):137-42.