Cross-recognition of a pit viper (Crotalinae) polyspecific antivenom explored through high-density peptide microarray epitope mapping
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 antive...
| Main Authors: | , , , , , , |
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| Format: | Artículo |
| Language: | Inglés |
| Published: |
2018
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| Subjects: | |
| Online Access: | http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005768 https://hdl.handle.net/10669/74786 |
| Summary: | 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. |
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