A new neutralizing antibody against botulinum neurotoxin B recognizes the protein receptor binding sites for synaptotagmins II.
Botulinum neurotoxins (BoNts) pose a biological hazard to humans and a serious potential bioweapon threat. Given the safety concern regarding the currently used equine antitoxin therapy for botulism, it is imperative to develop agents that are effective binding inhibitors. The aim of this study was to identify a novel neutralizing antibody against botulinum neurotoxin B (BoNtb) that recognizes the protein receptor binding sites for synaptotagmins II. This antibody showed significant dose-dependent protection against lethal toxin challenge in vivo at an intraperitoneal (i.p.) dose 10 times the half lethal dose (LD50). We proved that the efficacy of SC12 was based on its counteraction on the recognition and binding of BoNtb to target cells, resulting from the combination of antibody with the high affinity (KD: 1.34 nM) to protein receptor binding sites of BoNt by targeting a 25-mer dominant antigenic site on Hcc region (residues 1253-1277). The structure of the site targeted by this antibody overlaps the pocket-like protein receptor binding sites located at the distal tip of toxin molecule. Information gained from this study will facilitate the development of potent inhibitors that prevent the binding of BoNts with its receptors.
Wang
Hui
H
State Key Laboratory of Pathogens and Biosecurity, Institute of Microbiology and Epidemiology, No.20 Dongdajie, Fengtai District, Beijing 100071, PR China. geno0109@vip.sina.com
Li
Tao
T
Shi
Jing
J
Cai
Kun
K
Hou
Xiaojun
X
Wang
Qin
Q
Xiao
Le
L
Tu
Wei
W
Liu
Hao
H
Gao
Xiang
X
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000627:therapeutic use; D000992:Antitoxins / Q000276:immunology* / Q000627:therapeutic use; D001665:Binding Sites; D001905:Botulinum Toxins / Q000037:antagonists & inhibitors* / Q000276:immunology*; D019274:Botulinum Toxins, Type A; D001906:Botulism / Q000517:prevention & control; D002460:Cell Line; D018604:Epitope Mapping; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D051381:Rats; D050861:Synaptotagmin II / Q000378:metabolism*
D057134:Antibodies, Neutralizing; D000992:Antitoxins; D050861:Synaptotagmin II; C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A