Abstract：
:Concern about the malicious applications of botulinum neurotoxin has highlighted the need for a new generation of safe and highly potent antitoxins. In this study, we developed and evaluated the preclinical pharmacology and safety of a new F(ab')₂ antitoxin against botulinum neurotoxin serotype A (BoNT/A). As an alternative to formalin-inactivated toxoid, the recombinant Hc domain of botulinum neurotoxin serotype A (rAHc) was used to immunize horses, and the IgGs from the hyperimmune sera were digested to obtain F(ab')₂ antitoxin. The protective effect of the new F(ab')₂ antitoxin against BoNT/A was determined both in vitro and in vivo. The results showed that the F(ab')₂ antitoxin could prevent botulism in mice challenged with BoNT/A and effectively delayed progression of paralysis from botulism in the therapeutic setting. The preclinical safety of the new F(ab')₂ antitoxin was also evaluated, and it showed neither harmful effects on vital functions nor adverse effects such as acute toxicity, or immunological reactions in mice and dogs. Thus, our results provide valuable experimental data for this new antitoxin as a potential candidate for treatment of botulism caused by BoNT/A, and our findings support the safety of the new F(ab')₂ antitoxin for clinical use. Our study further demonstrates the proof of concept for development of a similar strategy for obtaining potent antitoxin against other BoNT serotypes.
journal_name
Biochimiejournal_title
Biochimieauthors
Yu YZ,Zhang SM,Wang WB,Du Y,Zhu HQ,Wang RL,Zhou XW,Lin JB,Wang S,Yu WY,Huang PT,Sun ZWdoi
10.1016/j.biochi.2010.06.010subject
Has Abstractpub_date
2010-10-01 00:00:00pages
1315-20issue
10eissn
0300-9084issn
1638-6183pii
S0300-9084(10)00224-5journal_volume
92pub_type
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