Abstract
Botulinum neurotoxins (BoNTs), the causative agents for life-threatening human disease botulism, have been recognized as biological warfare agents. In this study, a neutralizing mouse monoclonal antibody against botulinum neurotoxin serotype B (BoNT/B), named BTBH-N1, was developed from mice immunized with BoNT/B toxoid without non-toxic components, which are generally associated with the toxin. Western blot analysis, using recombinant toxin fragments containing light (L), N-terminal half of heavy (HN) and C-terminal half of heavy chains, indicated that BTBH-N1 recognizes linear epitopes located on the HN domain. An in vivo neutralization assay with mice, was conducted to characterize the neutralization capacity of the BTBH-N1. Only 10 microg of BTBH-N1 completely neutralized 20 units (1 unit = one 50% lethal dose) of BoNT/B. Even though the Mab (up to 100 microg) failed to protect mice challenged with 100 units, it significantly prolonged the time to death in a dose dependent manner. BTBH-N1, the first neutralizing antibody against BoNT/B, could be further developed as effective biological therapeutics for preventing and treating botulism, as well as other diseases caused by BoNT/B.
References
Jul 1, 1976·European Journal of Immunology·G Köhler, C Milstein
Aug 15, 1985·European Journal of Biochemistry·C C ShoneJ Melling
Mar 18, 1985·Journal of Immunological Methods·B FriguetM E Goldberg
Jan 1, 1982·Pharmacology & Therapeutics·G Sakaguchi
Mar 20, 1980·Biochimica Et Biophysica Acta·M KitamuraY Nagai
Sep 1, 1994·Toxicology and Applied Pharmacology·L B PearceR D MacCallum
Aug 1, 1995·Protein Science : a Publication of the Protein Society·M Oblatt-MontalM Montal
Nov 1, 1995·Quarterly Reviews of Biophysics·C Montecucco, G Schiavo
Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·M MatteoliC Montecucco
Nov 1, 1996·Vaccine·M T Dertzbaugh, M W West
Dec 5, 1997·Hybridoma·D R BrownJ J Schmidt
Oct 31, 1998·Vaccine·S BavariM A Olson
Dec 19, 2000·Infection and Immunity·D D PlessS Bavari
Mar 7, 2001·JAMA : the Journal of the American Medical Association·S S ArnonUNKNOWN Working Group on Civilian Biodefense
Jun 27, 2001·Applied and Environmental Microbiology·H C WuC C Lung
Sep 13, 2001·Infection and Immunity·B P MullaneyJ D Marks
Jun 4, 2002·Nature Biotechnology·Jennifer A MaynardGeorge Georgiou
Aug 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·A NowakowskiJ D Marks
Dec 3, 2002·Nature Structural Biology·Lilia K Koriazova, Mauricio Montal
Citations
Dec 12, 2007·Infection and Immunity·Michael R BaldwinJoseph T Barbieri
Jun 3, 2008·Applied and Environmental Microbiology·Reuven Rasooly, Paula M Do
Nov 26, 2010·The Journal of Pharmacology and Experimental Therapeutics·Md EliasLance L Simpson
Feb 26, 2008·Hybridoma·Myung-Shin LeeJunho Chung
May 26, 2009·Applied Biochemistry and Biotechnology·Wei-Gang HuLes P Nagata
Feb 7, 2008·Expert Review of Vaccines·Laura M ZarebskiAlessandro Sette
Aug 6, 2008·Journal of Pharmaceutical Sciences·Christina VesselyJohn F Carpenter
May 24, 2007·Journal of Pharmaceutical Sciences·Christina VesselyJohn F Carpenter
Feb 11, 2014·Analytical Chemistry·Seok Joon KwonKyung Bok Lee
Oct 11, 2008·Angewandte Chemie·Bert WillisKim D Janda
Aug 28, 2012·Toxicon : Official Journal of the International Society on Toxinology·Alexey ZdanovskyMaria Zdanovskaia
Jul 5, 2012·PloS One·Yao ZhaoJinglin Wang
Jan 30, 2014·PloS One·Eran DiamantRan Zichel
Nov 30, 2006·Immunology and Cell Biology·Yi-Hua ZhouSuzanne U Emerson
Jun 12, 2013·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Daniel E Forman, Richert E Goyette
Jul 24, 2012·Toxins·Siu-Kei Chow, Arturo Casadevall
May 13, 2020·Toxins·Takuhiro MatsumuraYukako Fujinaga