Journal article
Cross-recognition of a pit viper (Crotalinae) polyspecific antivenom explored through high-density peptide microarray epitope mapping
Network Engineering of Eukaryotic Cell factories, Section for Synthetic Biology, Department of Biotechnology and Biomedicine, Technical University of Denmark1
Department of Bio and Health Informatics, Technical University of Denmark2
Genomic Epidemiology, Department of Bio and Health Informatics, Technical University of Denmark3
University of Costa Rica4
Department of Biotechnology and Biomedicine, Technical University of Denmark5
Integrative Systems Biology, Department of Bio and Health Informatics, Technical University of Denmark6
Snakebite antivenom is a 120 years old invention based on polyclonal mixtures of antibodies purified from the blood of hyper-immunized animals. Knowledge on antibody recognition sites (epitopes) on snake venom proteins is limited, but may be used to provide molecular level explanations for antivenom cross-reactivity.
In turn, this may help guide antivenom development by elucidating immunological biases in existing antivenoms. In this study, we have identified and characterized linear elements of B-cell epitopes from 870 pit viper venom protein sequences by employing a high-throughput methodology based on custom designed high-density peptide microarrays.
By combining data on antibody-peptide interactions with multiple sequence alignments of homologous toxin sequences and protein modelling, we have determined linear elements of antibody binding sites for snake venom metalloproteases (SVMPs), phospholipases A2s (PLA2s), and snake venom serine proteases (SVSPs).
The studied antivenom antibodies were found to recognize linear elements in each of the three enzymatic toxin families. In contrast to a similar study of elapid (non-enzymatic) neurotoxins, these enzymatic toxins were generally not recognized at the catalytic active site responsible for toxicity, but instead at other sites, of which some are known for allosteric inhibition or for interaction with the tissue target.
Antibody recognition was found to be preserved for several minor variations in the protein sequences, although the antibody-toxin interactions could often be eliminated completely by substitution of a single residue. This finding is likely to have large implications for the cross-reactivity of the antivenom and indicate that multiple different antibodies are likely to be needed for targeting an entire group of toxins in these recognized sites.
Language: | English |
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Publisher: | Public Library of Science |
Year: | 2017 |
Pages: | e0005768 |
ISSN: | 19352735 and 19352727 |
Types: | Journal article |
DOI: | 10.1371/journal.pntd.0005768 |
ORCIDs: | Engmark, Mikael , Laustsen, Andreas Hougaard , De Masi, Federico , Andersen, Mikael Rørdam and Lund, Ole |
Animals Antivenins Arctic medicine. Tropical medicine Cross Reactions Crotalid Venoms Epitope Mapping Epitopes, B-Lymphocyte Humans Metalloproteases Microarray Analysis Phospholipases A2 Public aspects of medicine RA1-1270 RC955-962 Sequence Alignment Snake Bites Structural Homology, Protein Viperidae