title: A natural human IgM antibody that neutralizes botulinum neurotoxin in vivo.
abstract: Affinity-matured human antibodies have demonstrated efficacy as countermeasures for exposure to botulinum neurotoxin (BoNT), which is the cause of the disease botulism category A select bioterror agent. Little is known, however, about the potential role of natural (un-mutated) antibodies in the protective immune response to BoNT. Here we describe the cloning of two human IgM antibodies that bind serotype A BoNT. Both are un-mutated IgM antibodies, consistent with an origin in naive B cells. One of the antibodies is able to fully neutralize a lethal dose of serotype A BoNT in vivo. These results suggest that the natural human antibody repertoire may play a role in protection from exposure to biological toxins.
authors.affiliation: Cardeza Foundation for Hematologic Research and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Sharad P
authors.initials: SP
authors.lastname: Adekar
authors.forename: Fetweh H
authors.initials: FH
authors.lastname: Al-Saleem
authors.forename: M D
authors.initials: MD
authors.lastname: Elias
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Rybinski
authors.forename: Lance L
authors.initials: LL
authors.lastname: Simpson
authors.forename: Scott K
authors.initials: SK
authors.lastname: Dessain
mesh_terms: D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D001666:Binding Sites, Antibody; D001905:Botulinum Toxins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D019274:Botulinum Toxins, Type A / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D001906:Botulism / Q000276:immunology / Q000517:prevention & control; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003014:Clostridium botulinum / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data
chemical_list: D000907:Antibodies, Bacterial; D007075:Immunoglobulin M; C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A