期刊
TOXICON
卷 138, 期 -, 页码 151-158出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2017.08.028
关键词
Epitope mapping; Single toxin immunization; Three-finger toxin; Short neurotoxin; Dendroaspis polylepis
资金
- Novo Nordisk Fonden [NNF130C0005613, NNF160C0019248]
- Drug Research Academy (University of Copenhagen)
- Dansk Tennis Fond
- Oticon Fonden
- Knud Hojgaards Fond
- Rudolph Als Fondet
- Henry Shaws Legat
- Lge Johannes Nicolai Krogsgaard og Hustru Else Krogsgaards Mindelegat for Medicinsk Forskning og Medicinske Studenter ved Kobenhavns Universitet
- Lundbeckfonden
- Torben og Alice Frimodts Fond
- Frants Allings Legat
- Christian og Ottilia Brorsons Rejselegat for Yngre Videnskabsmnd-og kvinder
- Fonden for Lgevidenskabens Fremme
- Novo Nordisk Fonden [NNF16OC0019248, NNF13OC0005613] Funding Source: researchfish
Polyvalent snakebite antivenoms derive their therapeutic success from the ability of their antibodies to neutralize venom toxins across multiple snake species. This ability results from a production process involving immunization of large mammals with a broad suite of toxins present in venoms. As a result of immunization with this wide range of toxins, many polyvalent antivenoms have a high degree of cross reactivity to similar toxins in other snake venoms a cross-reactivity which cannot easily be deconvoluted. As a proof of concept, we aimed at exploring the opposite scenario by performing a high-throughput evaluation of the extent of cross-reactivity of a polyclonal mixture of antibodies that was raised against only a single snake venom fraction. For this purpose, a venom fraction containing short neurotoxin 1 (SN-1; Uniprot accession number P01416, three-finger toxin (3FTx) family), which is the medically most important toxin from the notorious black mamba (Dendroaspis polylepis), was employed. Following immunization of a rabbit, a specific polyclonal antibody response was confirmed by ELISA and immunodiffusion. Subsequently, these antibodies were investigated by high-density peptide microarray to reveal linear elements of recognized epitopes across 742 3FTxs and 10 dendrotoxins. This exploratory study demonstrates in a single immunized animal that cross-reactivity between toxins of high similarity may be difficult to obtain when immunizing with a single 3FTx containing venom fraction. Additionally, this study explored the influence of employing different lengths of peptides in high-density peptide microarray experiments for identification of toxin epitopes. Using 8-mer, 12-mer, and 15-mer peptides, a single linear epitope element was identified in SN-1 with high precision. (C) 2017 Elsevier Ltd. All rights reserved.
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