Camelid VHH Antibodies that Neutralize Botulinum Neurotoxin Serotype E Intoxication or Protease Function

被引:17
|
作者
Tremblay, Jacqueline M. [1 ]
Vazquez-Cintron, Edwin [2 ]
Lam, Kwok-Ho [3 ]
Mukherjee, Jean [1 ]
Bedenice, Daniela [4 ]
Ondeck, Celinia A. [2 ]
Conroy, Matthieu T. [2 ]
Bodt, Skylar M. L. [2 ]
Winner, Brittany M. [2 ]
Webb, Robert P. [5 ]
Ichtchenko, Konstantin [6 ]
Jin, Rongsheng [3 ]
McNutt, Patrick M. [2 ]
Shoemaker, Charles B. [1 ]
机构
[1] Tufts Univ, Cummings Sch Vet Med, Dept Infect Dis & Global Hlth, North Grafton, MA 01536 USA
[2] US Army, Med Res Inst Chem Def, Aberdeen Proving Ground, MD 21010 USA
[3] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA
[4] Tufts Univ, Cummings Sch Vet Med, Dept Clin Sci, North Grafton, MA 01536 USA
[5] US Army, Med Res Inst Infect Dis, Bacteriol Div, Ft Detrick, MD 21702 USA
[6] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA
关键词
botulinum neurotoxin; botulism; toxin; antitoxin; single-domain antibody; VHH; neutralization; protease; SINGLE; BINDING; NANOBODIES; AGENTS; CHALLENGE; PROTECTS; DOMAINS; TOXINS; MICE; PH;
D O I
10.3390/toxins12100611
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Botulinum neurotoxin (BoNT) serotype E is one of three serotypes that cause the preponderance of human botulism cases and is a Tier 1 Select Agent. BoNT/E is unusual among BoNT serotypes for its rapid onset and short duration of intoxication. Here we report two large panels of unique, unrelated camelid single-domain antibodies (VHHs) that were selected for their ability to bind to BoNT/E holotoxin and/or to the BoNT/E light chain protease domain (LC/E). The 19 VHHs which bind to BoNT/E were characterized for their subunit specificity and 8 VHHs displayed the ability to neutralize BoNT/E intoxication of neurons. Heterodimer antitoxins consisting of two BoNT/E-neutralizing VHHs, including one heterodimer designed using structural information for simultaneous binding, were shown to protect mice against co-administered toxin challenges of up to 500 MIPLD50. The 22 unique VHHs which bind to LC/E were characterized for their binding properties and 9 displayed the ability to inhibit LC/E protease activity. Surprisingly, VHHs selected on plastic-coated LC/E were virtually unable to recognize soluble or captured LC/E while VHHs selected on captured LC/E were poorly able to recognize LC/E coated to a plastic surface. This panel of anti-LC/E VHHs offer insight into BoNT/E function, and some may have value as components of therapeutic antidotes that reverse paralysis following BoNT/E exposures.
引用
收藏
页数:18
相关论文
共 50 条
  • [1] In Vivo Neutralization of Botulinum Neurotoxins Serotype E with Heavy-chain Camelid Antibodies (VHH)
    Hamid Bakherad
    Seyed Latif Mousavi Gargari
    Iraj Rasooli
    Masoumeh RajabiBazl
    Mohammad Mohammadi
    Walead Ebrahimizadeh
    Leila Safaee Ardakani
    Hamed Zare
    Molecular Biotechnology, 2013, 55 : 159 - 167
  • [2] In Vivo Neutralization of Botulinum Neurotoxins Serotype E with Heavy-chain Camelid Antibodies (VHH)
    Bakherad, Hamid
    Gargari, Seyed Latif Mousavi
    Rasooli, Iraj
    RajabiBazl, Masoumeh
    Mohammadi, Mohammad
    Ebrahimizadeh, Walead
    Ardakani, Leila Safaee
    Zare, Hamed
    MOLECULAR BIOTECHNOLOGY, 2013, 55 (02) : 159 - 167
  • [3] Two VHH Antibodies Neutralize Botulinum Neurotoxin E1 by Blocking Its Membrane Translocation in Host Cells
    Lam, Kwok-Ho
    Perry, Kay
    Shoemaker, Charles B.
    Jin, Rongsheng
    TOXINS, 2020, 12 (10)
  • [4] Algal chloroplast produced camelid VHH antitoxins are capable of neutralizing botulinum neurotoxin
    Barrera, Daniel J.
    Rosenberg, Julian N.
    Chiu, Joanna G.
    Chang, Yung-Nien
    Debatis, Michelle
    Ngoi, Soo-Mun
    Chang, John T.
    Shoemaker, Charles B.
    Oyler, George A.
    Mayfield, Stephen P.
    PLANT BIOTECHNOLOGY JOURNAL, 2015, 13 (01) : 117 - 124
  • [5] Monoclonal antibodies against botulinum neurotoxin serotype F
    Fan, Y.
    Lou, J.
    Garcia, C.
    Zhai, W.
    Dong, J.
    Wen, W.
    Conrad, F.
    Brown, J.
    Skerry, J.
    Smith, T. J.
    Smith, L. A.
    Marks, J. D.
    TOXICON, 2013, 68 : 85 - 86
  • [6] HUMAN-DERIVED MONOCLONAL ANTIBODIES EFFECTIVELY NEUTRALIZE BOTULINUM NEUROTOXIN
    Matsumura, Takuhiro
    Amatsu, Sho
    Yutani, Masahiro
    Fujinaga, Yukako
    TOXICON, 2018, 156 : S79 - S79
  • [7] Antibody protection of mice from botulinum neurotoxin serotype B intoxication
    Cheng, L. W.
    Stanker, L. H.
    Henderson, T. D., II
    Scotcher, M. C.
    TOXICON, 2013, 68 : 83 - 84
  • [8] Development of immunodetection system for botulinum neurotoxin serotype E
    Sarita, R.
    Ponmariappan, Sarkaraisamy
    Sharma, Arti
    Kamboj, Dev Vrat
    Jain, A. K.
    INDIAN JOURNAL OF MEDICAL RESEARCH, 2018, 147 : 603 - 610
  • [9] Chirality Holds the Key for Potent Inhibition of the Botulinum Neurotoxin Serotype A Protease
    Stowe, G. Neil
    Silhar, Peter
    Hixon, Mark S.
    Silvaggi, Nicholas R.
    Allen, Karen N.
    Moe, Scott T.
    Jacobson, Alan R.
    Barbieri, Joseph T.
    Janda, Kim D.
    ORGANIC LETTERS, 2010, 12 (04) : 756 - 759
  • [10] Solubility of the catalytic domains of Botulinum neurotoxin serotype E subtypes
    Chen, Sheng
    Barbieri, Joseph T.
    PROTEIN EXPRESSION AND PURIFICATION, 2016, 118 : 18 - 24