Abstract
BackgroundBotulinum 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.Methods and FindingsWe 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.ConclusionsThe 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.
Highlights
Botulinum neurotoxins (BoNTs) comprise a group of highly lethal toxins consisting of 7 serotypes (BoNT/A-G) produced by the anerobic bacteria, Clostridium botulinum [1,2]
The light chain (LC) act as zinc metallopeptidases, which solely hydrolyze one of three SNARE proteins depending on the serotype: BoNT A and E cleave synaptosomal-associated protein of 25 kDa and BoNT/B and F cleave the vesicle associated membrane protein (VAMP) [6,7,8,9]. resulting in a blockade of neurotransmission and flaccid paralysis [10]
The reconstructed Hc proteins were expressed in E.coli BL21 (DE3) in soluble form and purified for preparation of a toxoid immunogen
Summary
Botulinum neurotoxins (BoNTs) comprise a group of highly lethal toxins consisting of 7 serotypes (BoNT/A-G) produced by the anerobic bacteria, Clostridium botulinum [1,2]. Four of the BoNT serotypes (A, B, E, and F) cause human botulism, a neuroparalytic disease which results from ingestion of pre-formed toxin present in contaminated food and from toxin produced in vivo from infected wounds [3]. Owing to their extreme potency and lethality, BoNTs are included in the list of category A select agents and toxins [4]. The binding domain initially interacts with low affinity to a group of gangliosides on the presynaptic plasma membrane [12], after which it binds to a protein acceptor. The confirmation of key epitopes with development of effective mAb is urgently needed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
