title: Potent neutralization of botulinum neurotoxin/B by synergistic action of antibodies recognizing protein and ganglioside receptor binding domain.
abstract: BACKGROUND
  Botulinum neurotoxins (BoNTs), the causative agents for life-threatening human disease botulism, have been recognized as biological warfare agents. Monoclonal antibody (mAb) therapeutics hold considerable promise as BoNT therapeutics, but the potencies of mAbs against BoNTs are usually less than that of polyclonal antibodies (or oligoclonal antibodies). The confirmation of key epitopes with development of effective mAb is urgently needed.
  
  
  RESULTS
  We selected 3 neutralizing mAbs which recognize different non-overlapping epitopes of BoNT/B from a panel of neutralizing antibodies against BoNT/B. By comparing the neutralizing effects among different combination groups, we found that 8E10, response to ganglioside receptor binding site, could synergy with 5G10 and 2F4, recognizing non-overlapping epitopes within Syt II binding sites. However, the combination of 5G10 with 2F4 blocking protein receptor binding sites did not achieve synergistical effects. Moreover, we found that the binding epitope of 8E10 was conserved among BoNT A, B, E, and F, which might cross-protect the challenge of different serotypes of BoNTs in vivo.
  
  
  CONCLUSIONS
  The combination of two mAbs recognizing different receptors' binding domain in BoNTs has a synergistic effect. 8E10 is a potential universal partner for the synergistical combination with other mAb against protein receptor binding domain in BoNTs of other serotypes.
authors.affiliation: School of Pharmacy, The Center for Antibody Medicine of Ministry of Education, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Chen
authors.forename: Shuhui
authors.initials: S
authors.lastname: Wang
authors.forename: Huajing
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Mao
authors.forename: Tiancheng
authors.initials: T
authors.lastname: Zhang
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ji
authors.forename: Xin
authors.initials: X
authors.lastname: Shi
authors.forename: Tian
authors.initials: T
authors.lastname: Xia
authors.forename: Weijia
authors.initials: W
authors.lastname: Lu
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Dai
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000918:Antibody Specificity; D001665:Binding Sites; D001905:Botulinum Toxins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D019274:Botulinum Toxins, Type A; D017124:Conserved Sequence; D018604:Epitope Mapping; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D011956:Receptors, Cell Surface; C034993:ganglioside receptor; C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A