Plug and play virus-like particles for the generation of anti-toxin antibodies DOI Creative Commons
Rebecca J. Edge, Amy E. Marriott,

Emma Stars

et al.

Toxicon X, Journal Year: 2024, Volume and Issue: 23, P. 100204 - 100204

Published: Aug. 26, 2024

Snakebite is a major global health concern, for which antivenom remains the only approved treatment to neutralise harmful effects of toxins. However, some medically important toxins are poorly immunogenic, resulting in reduced efficacy final product. Boosting immunogenicity these commercial immunising mixtures could be an effective strategy improve dose efficacy, and displaying snake antigens on Virus-like particles (VLPs) one method this. despite applications field snakebite, VLPs have yet explored methods that practical at manufacturing scale. Here we describe utilisation "plug play" VLP system display immunogenic linear peptide epitopes from three finger (3FTxs) generate anti-toxin antibodies. Rabbits were immunised with individual consensus their antibody responses characterised by immunoassay. Of experimental sequences, two produced antibodies capable recognising peptides, whilst also recognise native whole Further characterisation raised against this demonstrated sub-class specific response, able elicit partially neutralising responses, increased survival times murine snakebite envenoming model.

Language: Английский

Revolutionizing snakebite care with novel antivenoms: Breakthroughs and barriers DOI Creative Commons

Samuel Odo Uko,

Ibrahim Malami, Kasimu Ghandi Ibrahim

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(3), P. e25531 - e25531

Published: Jan. 30, 2024

Snakebite envenoming (SBE) is a global public health concern, primarily due to the lack of effective antivenom for treating snakebites inflicted by medically significant venomous snakes prevalent across various geographic locations. The rising demand safe, cost-effective, and potent snakebite treatments highlights urgent need develop alternative therapeutics targeting relevant toxins. This development could provide promising discoveries create novel recombinant solutions, leveraging human monoclonal antibodies, synthetic peptides nanobodies. Such technologies as DNA, peptide epitope mapping phage display etc) have potential exceed traditional use equine polyclonal which long been used in production. Recombinant can be engineered target certain toxins that play critical role pathology. approach has produce with improved efficacy safety profiles. However, there are limitations challenges associated these emerging technologies. Therefore, identifying overcoming optimizing antivenoms. review aimed at presenting thorough overview diverse antivenom, emphasizing their offering insights into prospects advancing

Language: Английский

Citations

9
Recent advancements in snake antivenom production DOI
Anurag S. Rathore, Ramesh Kumar, Om Shanker Tiwari

et al.

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 240, P. 124478 - 124478

Published: April 25, 2023

Language: Английский

Citations

14
Metabolomics and proteomics: synergistic tools for understanding snake venom inhibition DOI
S. Hussain, Danie Kingsley

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Language: Английский

Citations

0
Exploring the Utility of ssDNA Aptamers Directed against Snake Venom Toxins as New Therapeutics for Snakebite Envenoming DOI Creative Commons
Nessrin Alomran, Raja Chinnappan, Jaffer Alsolaiss

et al.

Toxins, Journal Year: 2022, Volume and Issue: 14(7), P. 469 - 469

Published: July 8, 2022

Snakebite is a neglected tropical disease that causes considerable death and disability in the world. Although snakebite can cause variety of pathologies victims, haemotoxic effects are particularly common typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Antivenoms mainstay therapy for treating toxic snakebite, but despite saving thousands lives annually, these therapies associated with limited cross-snake species efficacy due to venom variation, which ultimately restricts their therapeutic utility particular geographical regions. In this study, we sought explore potential ssDNA aptamers as toxin-specific inhibitory alternatives antibodies. As proof principle model, selected snake serine protease toxins, responsible contributing coagulopathy following envenoming, our target. Using SELEX technology, against recombinantly expressed versions fibrinogenolytic SVSPs ancrod from C. rhodostoma batroxobin B. atrox. From resulting pool specific directed each target, identified candidates exhibited low nanomolar binding affinities targets. Downstream aptamer-linked immobilised sorbent assay, fibrinogenolysis, coagulation profiling experiments demonstrated candidate were able recognise native recombinant SVSP toxins inhibit toxin- prolongation plasma clotting times fibrinogen, potencies highly comparable commercial polyvalent antivenoms. Our findings demonstrate rationally exhibit broad vitro cross-reactivity toxin isoforms found different venoms capable inhibiting pathologically relevant ex vivo models activity. These data highlight novel toxin-inhibiting therapeutics value tackling envenoming.

Language: Английский

Citations

15
Advanced Situation with Recombinant Toxins: Diversity, Production and Application Purposes DOI Open Access
Елена Ефременко, Aysel Aslanli, Ilya Lyagin

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4630 - 4630

Published: Feb. 27, 2023

Today, the production and use of various samples recombinant protein/polypeptide toxins is known actively developing. This review presents state-of-the-art in research development such their mechanisms action useful properties that have allowed them to be implemented into practice treat medical conditions (including oncology chronic inflammation applications) diseases, as well identify novel compounds detoxify by diverse approaches enzyme antidotes). Special attention given problems possibilities toxicity control obtained proteins. The prions are discussed frame possible detoxification enzymes. discusses feasibility obtaining variants form protein molecules modified with fluorescent proteins, affine sequences genetic mutations, allowing us investigate toxins’ bindings natural receptors.

Language: Английский

Citations

9
A single-chain variable fragment selected against a conformational epitope of a recombinantly produced snake toxin using phage display DOI Creative Commons
Charlotte Rimbault, Pelle D. Knudsen,

Anna Damsbo

et al.

New Biotechnology, Journal Year: 2023, Volume and Issue: 76, P. 23 - 32

Published: April 8, 2023

Phage display technology is a powerful tool for selecting monoclonal antibodies against diverse set of antigens. Within toxinology, however, it remains challenging to generate many animal toxins, as they are difficult obtain from venom. Recombinant toxins have been proposed solution overcome this challenge, but so far, few used antigens neutralizing antibodies. Here, we describe the recombinant expression α-cobratoxin in E. coli and its successful application an antigen phage selection campaign. From campaign, scFv (single-chain variable fragment) was isolated with similar binding affinity control generated native toxin. The selected recognizes structural epitope, enabling inhibit interaction between acetylcholine receptor toxin vitro. This approach represents first entirely vitro antibody strategy generating snake

Language: Английский

Citations

9
Harnessing the Cross-Neutralisation Potential of Existing Antivenoms for Mitigating the Outcomes of Snakebite in Sub-Saharan Africa DOI Open Access
Suyog Khochare, Anurag Jaglan,

U. Rashmi

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4213 - 4213

Published: April 11, 2024

Over 32,000 individuals succumb to snake envenoming in sub-Saharan Africa (sSA) annually. This results from several factors, including a lack of antivenom products capable neutralising the venoms diverse species this region. Most manufacturers produce polyvalent antivenoms targeting 3 16 clinically important sSA. However, specific are unavailable for many others, especially those with restricted geographic distribution. While next-generation antivenoms, comprising cocktail broadly antibodies, may offer an effective solution problem, given need their clinical validation, recombinant far being available snakebite victims. One strategies that could immediately address issue involves harnessing cross-neutralisation potential existing products. Therefore, we assessed neutralisation potency PANAF-Premium towards 14 medically snakes 13 countries across sSA which unavailable. Preclinical assays murine model revealed most under investigation were effectively neutralised by antivenom. Thus, finding highlights use treating bites and utility antivenoms.

Language: Английский

Citations

3
In vitro immunoreactivity and in vivo neutralization of Trimeresurus gracilis venom with antivenoms targeting four pit viper species DOI Creative Commons

Po‐Chun Chuang,

Jiawei Chen,

Yuen-Ying Chan

et al.

PLoS neglected tropical diseases, Journal Year: 2024, Volume and Issue: 18(3), P. e0012070 - e0012070

Published: March 25, 2024

Snakebite envenomation is a significant global health issue that requires specific antivenom treatments. In Taiwan, available antivenoms target variety of snakes, but none specifically Trimeresurus gracilis , an endemic and protected species found in the high mountain areas Taiwan. This study evaluated effectiveness existing against T . venom, focusing on bivalent developed for stejnegeri Protobothrops mucrosquamatu s (TsPmAV), as well monovalent Deinagkistrodon acutus (DaAV) Gloydius brevicaudus (GbAV). Our research involved vivo toxicity testing mice vitro immunobinding experiments using (chaotropic) enzyme-linked immunosorbent assays, comparing venoms from four pit viper ( P mucrosquamatus D ) with three types antivenoms. These findings indicate TsPmAV partially neutralized marginally surpassing efficacy DaAV. tests revealed GbAV displayed higher binding capacities toward venom than or Comparisons electrophoretic profiles also reveal has fewer snake C-type lectin like proteins more P-I metalloproteases phospholipase A 2 G highlights need current treatments show limited neutralizing local effects patients. provide crucial insights into clinical treatment protocols contribute to understanding evolutionary adaptation aiding development effective human health.

Language: Английский

Citations

2
Commercial Antivenoms Exert Broad Paraspecific Immunological Binding and In Vitro Inhibition of Medically Important Bothrops Pit Viper Venoms DOI Creative Commons
Jaffer Alsolaiss, Nessrin Alomran,

Laura Hawkins

et al.

Toxins, Journal Year: 2022, Volume and Issue: 15(1), P. 1 - 1

Published: Dec. 20, 2022

Snakebite envenoming is a life threatening neglected tropical disease that represents considerable public health concern in the tropics. Viperid snakes of genus Bothrops are among those greatest medical importance Latin America, and they frequently cause severe systemic haemotoxicity local tissue destructive effects human victims. Although snakebite antivenoms can be effective therapeutics, their efficacy undermined by venom toxin variation snake species. In this study we investigated extent paraspecific cross-reactivity exhibited three distinct anti-Bothrops (Soro antibotrópico-crotálico, BothroFav PoliVal-ICP) against seven different pit viper venoms from across America. We applied range vitro assays to assess immunological binding recognition toxins inhibitory activities specific functionalities. Our findings demonstrated that, despite some variations, monovalent antivenom polyvalent Soro antibotrópico-crotálico PoliVap-ICP extensive found venoms, with generally outperformed other two products. functional revealed outcomes largely consistent data, exhibiting potencies procoagulant fibrinogen-depleting activities, though potent inhibition metalloproteinase activities. Overall, our demonstrate broad levels paraspecificity, often highly comparable between used manufacture related species, even case BothroFav. suggest current clinical utility these could possibly expanded parts America currently suffer lack therapies.

Language: Английский

Citations

9
Importance of the Cysteine-Rich Domain of Snake Venom Prothrombin Activators: Insights Gained from Synthetic Neutralizing Antibodies DOI Creative Commons
Laëtitia Misson, Jeffrey T. Mindrebo, Quoc Tran

et al.

Toxins, Journal Year: 2024, Volume and Issue: 16(8), P. 361 - 361

Published: Aug. 15, 2024

Snake venoms are cocktails of biologically active molecules that have evolved to immobilize prey, but can also induce a severe pathology in humans bitten. While animal-derived polyclonal antivenoms the primary treatment for snakebites, they often limitations efficacy and cause adverse side effects. Building on recent efforts develop improved antivenoms, notably through monoclonal antibodies, requires comprehensive understanding venom toxins. Among these toxins, snake metalloproteinases (SVMPs) play pivotal role, particularly viper envenomation, causing tissue damage, hemorrhage coagulation disruption. One current challenges development neutralizing antibodies against SVMPs is large size protein lack existing knowledge epitopes. Here, we screened synthetic human antibody library isolate an SVMP from saw-scaled (genus

Language: Английский

Citations

1