Virus-like particles displaying conserved toxin epitopes stimulate polyspecific, murine antibody responses capable of snake venom recognition
Abstract Antivenom is currently the first-choice treatment for snakebite envenoming. However, only a low proportion of antivenom immunoglobulins are specific to venom toxins, resulting in poor dose efficacy and potency. We sought to investigate whether linear venom epitopes displayed on virus like p...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13376-x |
| _version_ | 1828760199751532544 |
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| author | Stefanie K. Menzies Charlotte A. Dawson Edouard Crittenden Rebecca J. Edge Steven R. Hall Jaffer Alsolaiss Mark C. Wilkinson Nicholas R. Casewell Robert A. Harrison Stuart Ainsworth |
| author_facet | Stefanie K. Menzies Charlotte A. Dawson Edouard Crittenden Rebecca J. Edge Steven R. Hall Jaffer Alsolaiss Mark C. Wilkinson Nicholas R. Casewell Robert A. Harrison Stuart Ainsworth |
| author_sort | Stefanie K. Menzies |
| collection | DOAJ |
| description | Abstract Antivenom is currently the first-choice treatment for snakebite envenoming. However, only a low proportion of antivenom immunoglobulins are specific to venom toxins, resulting in poor dose efficacy and potency. We sought to investigate whether linear venom epitopes displayed on virus like particles can stimulate an antibody response capable of recognising venom toxins from diverse medically important species. Bioinformatically-designed epitopes, corresponding to predicted conserved regions of group I phospholipase A2 and three finger toxins, were engineered for display on the surface of hepatitis B core antigen virus like particles and used to immunise female CD1 mice over a 14 weeks. Antibody responses to all venom epitope virus like particles were detectable by ELISA by the end of the immunisation period, although total antibody and epitope specific antibody titres were variable against the different epitope immunogens. Immunoblots using pooled sera demonstrated recognition of various venom components in a diverse panel of six elapid venoms, representing three continents and four genera. Insufficient antibody yields precluded a thorough assessment of the neutralising ability of the generated antibodies, however we were able to test polyclonal anti-PLA2 IgG from three animals against the PLA2 activity of Naja nigricollis venom, all of which showed no neutralising ability. This study demonstrates proof-of-principle that virus like particles engineered to display conserved toxin linear epitopes can elicit specific antibody responses in mice which are able to recognise a geographically broad range of elapid venoms. |
| first_indexed | 2024-12-11T01:10:15Z |
| format | Article |
| id | doaj.art-d2b63dd9aae448068dd6d52352b56bfc |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-11T01:10:15Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d2b63dd9aae448068dd6d52352b56bfc2022-12-22T01:26:05ZengNature PortfolioScientific Reports2045-23222022-07-0112111510.1038/s41598-022-13376-xVirus-like particles displaying conserved toxin epitopes stimulate polyspecific, murine antibody responses capable of snake venom recognitionStefanie K. Menzies0Charlotte A. Dawson1Edouard Crittenden2Rebecca J. Edge3Steven R. Hall4Jaffer Alsolaiss5Mark C. Wilkinson6Nicholas R. Casewell7Robert A. Harrison8Stuart Ainsworth9Centre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineCentre for Snakebite Research and Interventions, Liverpool School of Tropical MedicineAbstract Antivenom is currently the first-choice treatment for snakebite envenoming. However, only a low proportion of antivenom immunoglobulins are specific to venom toxins, resulting in poor dose efficacy and potency. We sought to investigate whether linear venom epitopes displayed on virus like particles can stimulate an antibody response capable of recognising venom toxins from diverse medically important species. Bioinformatically-designed epitopes, corresponding to predicted conserved regions of group I phospholipase A2 and three finger toxins, were engineered for display on the surface of hepatitis B core antigen virus like particles and used to immunise female CD1 mice over a 14 weeks. Antibody responses to all venom epitope virus like particles were detectable by ELISA by the end of the immunisation period, although total antibody and epitope specific antibody titres were variable against the different epitope immunogens. Immunoblots using pooled sera demonstrated recognition of various venom components in a diverse panel of six elapid venoms, representing three continents and four genera. Insufficient antibody yields precluded a thorough assessment of the neutralising ability of the generated antibodies, however we were able to test polyclonal anti-PLA2 IgG from three animals against the PLA2 activity of Naja nigricollis venom, all of which showed no neutralising ability. This study demonstrates proof-of-principle that virus like particles engineered to display conserved toxin linear epitopes can elicit specific antibody responses in mice which are able to recognise a geographically broad range of elapid venoms.https://doi.org/10.1038/s41598-022-13376-x |
| spellingShingle | Stefanie K. Menzies Charlotte A. Dawson Edouard Crittenden Rebecca J. Edge Steven R. Hall Jaffer Alsolaiss Mark C. Wilkinson Nicholas R. Casewell Robert A. Harrison Stuart Ainsworth Virus-like particles displaying conserved toxin epitopes stimulate polyspecific, murine antibody responses capable of snake venom recognition Scientific Reports |
| title | Virus-like particles displaying conserved toxin epitopes stimulate polyspecific, murine antibody responses capable of snake venom recognition |
| title_full | Virus-like particles displaying conserved toxin epitopes stimulate polyspecific, murine antibody responses capable of snake venom recognition |
| title_fullStr | Virus-like particles displaying conserved toxin epitopes stimulate polyspecific, murine antibody responses capable of snake venom recognition |
| title_full_unstemmed | Virus-like particles displaying conserved toxin epitopes stimulate polyspecific, murine antibody responses capable of snake venom recognition |
| title_short | Virus-like particles displaying conserved toxin epitopes stimulate polyspecific, murine antibody responses capable of snake venom recognition |
| title_sort | virus like particles displaying conserved toxin epitopes stimulate polyspecific murine antibody responses capable of snake venom recognition |
| url | https://doi.org/10.1038/s41598-022-13376-x |
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