Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms

被引:20
作者
Riano-Umbarila, Lidia [1 ]
Gomez-Ramirez, Ilse V. [2 ]
Ledezma-Candanoza, Luis M. [2 ]
Olamendi-Portugal, Timoteo [2 ]
Remi Rodriguez-Rodriguez, Everardo [2 ]
Fernandez-Taboada, Guillermo [2 ]
Possani, Lourival D. [2 ]
Becerril, Baltazar [2 ]
机构
[1] Univ Nacl Autonoma Mexico, Inst Biotecnol, CONACYT, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico
[2] UNAM, Inst Biotecnol, Dept Med Mol & Bioproc, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico
关键词
cross-neutralization; directed evolution; phage display; polyvalent antivenom; scFv; scorpion; AMINO-ACID-SEQUENCE; 2; TOXINS; CENTRUROIDES; ACTIVATION; PEPTIDES; SUFFUSUS; CHANNEL; PROTEIN;
D O I
10.3390/toxins11010032
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
The recombinant antibody fragments generated against the toxic components of scorpion venoms are considered a promising alternative for obtaining new antivenoms for therapy. Using directed evolution and site-directed mutagenesis, it was possible to generate a human single-chain antibody fragment with a broad cross-reactivity that retained recognition for its original antigen. This variant is the first antibody fragment that neutralizes the effect of an estimated 13 neurotoxins present in the venom of nine species of Mexican scorpions. This single antibody fragment showed the properties of a polyvalent antivenom. These results represent a significant advance in the development of new antivenoms against scorpion stings, since the number of components would be minimized due to their broad cross-neutralization capacity, while at the same time bypassing animal immunization.
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页数:17
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共 34 条
  • [1] ISOLATION AND CHARACTERIZATION OF 2 TOXINS FROM THE MEXICAN SCORPION CENTRUROIDES-LIMPIDUS-LIMPIDUS KARSCH
    ALAGON, AC
    GUZMAN, HS
    MARTIN, BM
    RAMIREZ, AN
    CARBONE, E
    POSSANI, LD
    [J]. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY, 1988, 89 (01): : 153 - 161
  • [2] Bowers K.J., 2006, P 2006 ACM IEEE SC 0, P1
  • [3] Cross-neutralizing human anti-poliovirus antibodies bind the recognition site for cellular receptor
    Chen, Zhaochun
    Fischer, Elizabeth R.
    Kouiavskaia, Diana
    Hansen, Bryan T.
    Ludtke, Steven J.
    Bidzhieva, Bella
    Makiya, Michelle
    Agulto, Liane
    Purcell, Robert H.
    Chumakov, Konstantin
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (50) : 20242 - 20247
  • [4] Emerging options for the management of scorpion stings
    Chippaux, Jean-Philippe
    [J]. DRUG DESIGN DEVELOPMENT AND THERAPY, 2012, 6 : 165 - 173
  • [5] Mechanism of Dengue Virus Broad Cross-Neutralization by a Monoclonal Antibody
    Cockburn, Joseph J. B.
    Sanchez, M. Erika Navarro
    Fretes, Nickolas
    Urvoas, Agathe
    Staropoli, Isabelle
    Kikuti, Carlos M.
    Coffey, Lark L.
    Arenzana-Seisdedos, Fernando
    Bedouelle, Hugues
    Rey, Felix A.
    [J]. STRUCTURE, 2012, 20 (02) : 303 - 314
  • [6] Overview of scorpion toxins specific for Na+ channels and related peptides:: biodiversity, structure-function relationships and evolution
    de la Vega, RCR
    Possani, LD
    [J]. TOXICON, 2005, 46 (08) : 831 - 844
  • [7] Cross-neutralization of influenza A viruses mediated by a single antibody loop
    Ekiert, Damian C.
    Kashyap, Arun K.
    Steel, John
    Rubrum, Adam
    Bhabha, Gira
    Khayat, Reza
    Lee, Jeong Hyun
    Dillon, Michael A.
    O'Neil, Ryann E.
    Faynboym, Aleksandr M.
    Horowitz, Michael
    Horowitz, Lawrence
    Ward, Andrew B.
    Palese, Peter
    Webby, Richard
    Lerner, Richard A.
    Bhatt, Ramesh R.
    Wilson, Ian A.
    [J]. NATURE, 2012, 489 (7417) : 526 - +
  • [8] Antidotes against venomous animals: State of the art and prospectives
    Espino-Solis, G. P.
    Riano-Umbarila, L.
    Becerril, B.
    Possani, L. D.
    [J]. JOURNAL OF PROTEOMICS, 2009, 72 (02) : 183 - 199
  • [9] Biosynthetic Oligoclonal Antivenom (BOA) for Snakebite and Next-Generation Treatments for Snakebite Victims
    Kini, R. Manjunatha
    Sidhu, Sachdev S.
    Laustsen, Andreas Hougaard
    [J]. TOXINS, 2018, 10 (12):
  • [10] Pros and cons of different therapeutic antibody formats for recombinant antivenom development
    Laustsen, Andreas H.
    Maria Gutierrez, Jose
    Knudsen, Cecilie
    Johansen, Kristoffer H.
    Bermudez-Mendez, Erick
    Cerni, Felipe A.
    Jurgensen, Jonas A.
    Ledsgaard, Line
    Martos-Esteban, Andrea
    Ohlenschlaeger, Mia
    Pus, Urska
    Andersen, Mikael R.
    Lomonte, Bruno
    Engmark, Mikael
    Pucca, Manuela B.
    [J]. TOXICON, 2018, 146 : 151 - 175