title: Novel application of an in vitro technique to the detection and quantification of botulinum neurotoxin antibodies.
abstract: Detection of Clostridium botulinum neurotoxin (BoNT) neutralising antibodies is currently achieved using the mouse lethality assay (MLA). This technique has provided the majority of the data for vaccine development and, with the increasing use of BoNT as a therapeutic agent, the MLA is the assay of choice to evaluate 'non-responder' antisera. However, the MLA is semi-quantitative and has an animal consumption rate that raises ethical concerns. The development of an alternative is therefore desirable. Here, we describe an in vitro neuronal release assay that may represent such an alternative in terms of both its sensitivity and ability to produce quantitative data. Initially recognised in the course of assessing a novel vaccine candidate, the suitability of this assay has been further explored using an International standard. The results support the conclusion that the detection of neutralising antibodies in human sera should be attempted using this method.
authors.affiliation: Centre for Applied Microbiology and Research, Health Protection Agency Porton Down, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.
authors.forename: Yper H J
authors.initials: YH
authors.lastname: Hall
authors.forename: John A
authors.initials: JA
authors.lastname: Chaddock
authors.forename: Hilary J
authors.initials: HJ
authors.lastname: Moulsdale
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Kirby
authors.forename: Frances C G
authors.initials: FC
authors.lastname: Alexander
authors.forename: James D
authors.initials: JD
authors.lastname: Marks
authors.forename: Keith A
authors.initials: KA
authors.lastname: Foster
mesh_terms: D000818:Animals; D000906:Antibodies / Q000032:analysis* / Q000276:immunology*; D001905:Botulinum Toxins / Q000276:immunology* / Q000494:pharmacology; D005998:Glycine / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology
chemical_list: D000906:Antibodies; D001905:Botulinum Toxins; D005998:Glycine