title: A human monoclonal antibody that binds serotype A botulinum neurotoxin.
abstract: Monoclonal antibodies have demonstrated significant potential as therapeutics for botulinum neurotoxin exposures. We previously described a hybridoma method for cloning native human antibodies that uses a murine myeloma cell line that ectopically expresses the human telomerase catalytic subunit gene (hTERT) and the murine interleukin-6 gene (mIL-6). Here we describe a heterohybridoma cell line that ectopically expresses mIL-6 and hTERT and has improved stability of hTERT expression. We fused this cell line to human peripheral blood B cells from a subject who had received the botulinum toxoid vaccine, cloning a high-affinity antibody (13A) specific for serotype A botulinum neurotoxin (BoNT/A). The 13A antibody is an affinity-matured, post-germinal center IgG(1) lambda antibody that has partial neutralization activity in vivo. 13A binds an epitope on BoNT/A that overlaps the binding epitope of an IgG antibody previously shown to fully neutralize a lethal dose of BoNT/A in vivo. The 13A antibody may be useful for diagnostic testing or for incorporation into an oligoclonal therapeutic to counteract BoNT/A exposure.
authors.affiliation: Cardeza Foundation for Hematologic Research and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Sharad P
authors.initials: SP
authors.lastname: Adekar
authors.forename: R Mark
authors.initials: RM
authors.lastname: Jones
authors.forename: M D
authors.initials: MD
authors.lastname: Elias
authors.forename: Fetweh H
authors.initials: FH
authors.lastname: Al-Saleem
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Root
authors.forename: Lance L
authors.initials: LL
authors.lastname: Simpson
authors.forename: Scott K
authors.initials: SK
authors.lastname: Dessain
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D019274:Botulinum Toxins, Type A / Q000276:immunology* / Q000378:metabolism; D002459:Cell Fusion; D045744:Cell Line, Tumor; D006801:Humans; D006825:Hybridomas; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin; D051379:Mice; D009101:Multiple Myeloma; D011485:Protein Binding; D019098:Telomerase / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D015850:Interleukin-6; C509186:TERT protein, human; D019098:Telomerase; D019274:Botulinum Toxins, Type A