Editorial on the Research TopicUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Ainsworth, Stuart

Chávez Olórtegui, Carlos

Kini, R. Manjunatha

Laustsen, Andreas Hougaard

Lomonte, Bruno

Frontiers in Immunology

English

Editorial on the Research Topic

Novel Immunotherapies Against Envenomings by Snakes and Other Venomous Animal

Lausten, AH

Lomonte, B

Kini, RM

Chavez-Olortegui, C

LSTM Online Archive

EDITORIALpublished: 22 May 2020doi: 10.3389/fimmu.2020.01004Frontiers in Immunology | www.frontiersin.org 1 May 2020 | Volume 11 | Article 1004Edited and reviewed by:Denise Doolan,James Cook University, Australia*Correspondence:Andreas Hougaard Laustsenahola@bio.dtu.dkStuart Ainsworthstuart.ainsworth@lstmed.ac.ukBruno Lomontebruno.lomonte@ucr.ac.crR. Manjunatha Kinidbskinim@nus.edu.sgCarlos Chávez-Olórteguiolortegi@icb.ufmg.brSpecialty section:This article was submitted toVaccines and Molecular Therapeutics,a section of the journalFrontiers in ImmunologyReceived: 15 April 2020Accepted: 28 April 2020Published: 22 May 2020Citation:Laustsen AH, Ainsworth S,Lomonte B, Kini RM andChávez-Olórtegui C (2020) Editorial:Novel Immunotherapies AgainstEnvenomings by Snakes and OtherVenomous Animals.Front. Immunol. 11:1004.doi: 10.3389/fimmu.2020.01004Editorial: Novel ImmunotherapiesAgainst Envenomings by Snakes andOther Venomous AnimalsAndreas Hougaard Laustsen 1*, Stuart Ainsworth 2*, Bruno Lomonte 3*,R. Manjunatha Kini 4,5* and Carlos Chávez-Olórtegui 6*1Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark, 2Centre for SnakebiteResearch & Interventions, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, 3 Facultad de Microbiología,Instituto Clodomiro Picado, Universidad de Costa Rica, San José, Costa Rica, 4Department of Biological Sciences, Facultyof Science, National University of Singapore, Singapore, Singapore, 5Department of Pharmacology, Yong Loo Lin School ofMedicine, National University of Singapore, Singapore, Singapore, 6Departamento de Bioquímica, Instituto de CiênciasBiológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilKeywords: venom, envenoming, antivenom, recombinant antivenom, toxin-neutralization, immunotherapy,antibody discovery, serotherapyEditorial on the Research TopicNovel Immunotherapies Against Envenomings by Snakes and Other Venomous AnimalsGlobally, several million people fall victim to animal envenomings each year. These envenomingsare caused by snakes, scorpions, spiders, bees, and other venomous animals (Pucca et al.), whichare able to inflict bites and stings, which inject venoms, mixtures of protein-based toxins, intotheir victims and prey. Since the late eighteenth century, the first-choice treatment for severeanimal envenomings has been antivenoms, which consist of polyclonal antibodies or antibodyfragments isolated from the serum or plasma of animals hyper-immunized with venoms. Theseessential medicines are invaluable in saving the lives and limbs of patients worldwide. However,these “conventional” antivenoms are burdened with a number of disadvantages, such as a highcontent of non-neutralizing antibodies, a propensity to induce adverse reactions (including serumsickness and anaphylaxis), and a relatively high cost of manufacture compared to many otherroutinely used therapeutics (1). In recent decades, many new biotechnologies have emerged,which have been successfully employed to develop breakthrough therapies within oncology,autoimmunity, and infectious diseases. These biotechnologies present an opportunity for thefield of envenoming therapy, and antivenom researchers have therefore started to apply thesenew approaches with the goal of increasing the efficacy of plasma-derived antivenoms throughinnovative immunization approaches (2), or by utilizing recombinant DNA technology andantibody discoverymethodologies to generate recombinant antivenoms with improved efficacy andsafety profiles.This Research Topic presents two reviews and two original research articles that exhibitprominent and recent examples of the developments within novel immunotherapies againstenvenomings by snakes and other venomous animals. In Pucca et al., the history of envenomingtherapies is reviewed with a focus on the key developments in the life sciences that led to thegeneration of the first antivenoms, as well as their subsequent refinement and optimization.It underscores the impact of basic immunological research within the field, as well asthe contributions generated within antivenom research, which led to the development ofimmunological methods and novel therapeutics based on monoclonal antibodies that are nowLaustsen et al. Editorial: Novel Immunotherapies Against Envenomingsutilized across almost all fields of medicine. This review furtherprovides perspectives on the advances in biotechnology in thelast decades, which have influenced the academic research agendain antivenom research, and discusses how different scientificbreakthroughs in synthetic biology, antibody technologies,immunology, and molecular biology, such as phage displaytechnology, may be exploited in the development of improved,next-generation envenoming therapies.In de Castro et al., an example is provided of how knowledgeof venom biology and new immunization approaches can beharnessed in the development of improved serotherapies againstenvenomings by Micrurus spp. (coral snakes). Here, a combinedimmunization protocol, using priming doses of M. frontalisvenom and booster doses of synthetic B-cell epitopes derivedfrom M. corallinus three-finger toxins and phospholipasesA2, elicited a humoral response against both venoms in arabbit model. The raised sera displayed relevant cross-reactivityagainst venoms from other Micrurus species (M. altirostris,M. lemniscatus, M. spixii, and M. surinamensis) and weredemonstrated to be able to neutralize PLA2 activity ofM. frontalisandM. corallinus venoms. In vivo, the sera completely protectedmice from a challenge with 1.5 median lethal dose (LD50) of M.corallinus venom and protected 50% of mice challenged with 1.5LD50 ofM. frontalis venom.Bailon-Calderon et al. describe a promising example ofthe utilization of antibody technologies. In their work, aset of nanobodies was developed from a library of a Lamaglama immunized with the venom of Bothrops atrox, aviperid of utmost medical relevance in South America.Several of the obtained recombinant nanobodies showedneutralizing ability toward hemorrhagic and myotoxic venomcomponents, which are responsible formajor local tissue damage.The study further highlights the valuable potential of theseinnovative biotherapeutics, bringing them one step closer toclinical application.Finally, Pucca et al. provide a comprehensive overview ofthe scientific literature surrounding bee venom toxinology andthe treatment against bee stings. Here, the epidemiology of Apisspp. (bees) is presented with a special focus on the speciesApis mellifera (Africanized bee), which is a hybrid species ofthe African and European honey bees that cause a significantnumber of severe envenomings, some of which have resulted inhuman fatalities. Further, all proteinaceous components of beevenom are presented with a discussion on the two main toxiccomponents, phospholipase A2 andmelittin, and their synergistictoxic function in victims. The review concludes with a detailingof how bee stings are currently only treated symptomatically, andthat opportunities exist for developing recombinant antivenomsagainst bee envenomings.The field of next-generation antivenoms has recently gainedincreased interest, and technological advancements now enableresearchers to undertake the ambitious endeavor of developingimproved therapeutic interventions against animal envenomings.This trend will likely continue for the years to come, as suchefforts are officially supported by the recently published strategyfrom the World Health Organization (3). Next-generationantivenom research is still a rather nascent field. However, withinthe next two decades, it is predicted that this area of research willexperience significant development and innovation.AUTHOR CONTRIBUTIONSAL prepared the first draft. All authors corrected the manuscriptand provided revisions.REFERENCES1. Kini RM, Sidhu SS, Laustsen AH. Biosynthetic oligoclonal antivenom (BOA)for snakebite and next-generation treatments for snakebite victims. Toxins.(2018) 10:534. doi: 10.3390/toxins101205342. Bermúdez-Méndez E, Fuglsang-Madsen A, Føns S, Lomonte B, Gutiérrez JM,Laustsen AH. Innovative immunization strategies for antivenom development.Toxins. (2018) 10:452. doi: 10.3390/toxins101104523. Williams DJ, Faiz MA, Abela-Ridder B, Ainsworth S, Bulfone TC, NickersonAD, et al. Strategy for a globally coordinated response to a priorityneglected tropical disease: snakebite envenoming. PLoS Negl Trop Dis. (2019)13:e0007059. doi: 10.1371/journal.pntd.0007059Conflict of Interest: The authors declare that the research was conducted in theabsence of any commercial or financial relationships that could be construed as apotential conflict of interest.Copyright © 2020 Laustsen, Ainsworth, Lomonte, Kini and Chávez-Olórtegui.This is an open-access article distributed under the terms of the CreativeCommons Attribution License (CC BY). The use, distribution or reproductionin other forums is permitted, provided the original author(s) and thecopyright owner(s) are credited and that the original publication in thisjournal is cited, in accordance with accepted academic practice. No use,distribution or reproduction is permitted which does not comply with theseterms.Frontiers in Immunology | www.frontiersin.org 2 May 2020 | Volume 11 | Article 1004

Editorial: Novel Immunotherapies Against Envenomings by Snakes and Other Venomous Animals

10.3389/fimmu.2020.01004Frontiers in Immunology11100

Laustsen, A.H.

Ainsworth, S.

Lomonte, B.

Kini, R.M.

Chávez-Olórtegui, C.

ScholarBank@NUS

Chavez-Olortegui, Carlos

Online Research Database In Technology

Repositorio Institucional de la Universidad de Costa Rica

Editorial: Novel immunotherapies against envenomings by snakes and other venomous animals

https://archive.lstmed.ac.uk/14639/1/Laustsen%20et%20al%202020_-Editorial%20Novel%20Immunotherapies_Frontiers-June-20.pdf

Editorial: Novel immunotherapies against envenomings by snakes and other venomous animals

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