History of Envenoming Therapy and Current Perspectives

Each year, millions of humans fall victim to animal envenomings, which may either be deadly or cause permanent disability to the effected individuals. The Nobel Prize-winning discovery of serum therapy for the treatment of bacterial infections (tetanus and diphtheria) paved the way for the introduct...

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Main Authors: Manuela B. Pucca, Felipe A. Cerni, Rahel Janke, Erick Bermúdez-Méndez, Line Ledsgaard, José E. Barbosa, Andreas H. Laustsen
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.01598/full
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author Manuela B. Pucca
Manuela B. Pucca
Felipe A. Cerni
Felipe A. Cerni
Rahel Janke
Erick Bermúdez-Méndez
Line Ledsgaard
José E. Barbosa
Andreas H. Laustsen
author_facet Manuela B. Pucca
Manuela B. Pucca
Felipe A. Cerni
Felipe A. Cerni
Rahel Janke
Erick Bermúdez-Méndez
Line Ledsgaard
José E. Barbosa
Andreas H. Laustsen
author_sort Manuela B. Pucca
collection DOAJ
description Each year, millions of humans fall victim to animal envenomings, which may either be deadly or cause permanent disability to the effected individuals. The Nobel Prize-winning discovery of serum therapy for the treatment of bacterial infections (tetanus and diphtheria) paved the way for the introduction of antivenom therapies for envenomings caused by venomous animals. These antivenoms are based on polyclonal antibodies derived from the plasma of hyperimmunized animals and remain the only specific treatment against animal envenomings. Following the initial development of serum therapy for snakebite envenoming by French scientists in 1894, other countries with high incidences of animal envenomings, including Brazil, Australia, South Africa, Costa Rica, and Mexico, started taking up antivenom production against local venomous animals over the course of the twentieth century. These undertakings revolutionized envenoming therapy and have saved innumerous patients worldwide during the last 100 years. This review describes in detail the above-mentioned historical events surrounding the discovery and the application of serum therapy for envenomings, as well as it provides an overview of important developments and scientific breakthroughs that were of importance for antibody-based therapies in general. This begins with discoveries concerning the characterization of antibodies, including the events leading up to the elucidation of the antibody structure. These discoveries further paved the way for other milestones in antibody-based therapies, such as the introduction of hybridoma technology in 1975. Hybridoma technology enabled the expression and isolation of monoclonal antibodies, which in turn formed the basis for the development of phage display technology and transgenic mice, which can be harnessed to directly obtain fully human monoclonal antibodies. These developments were driven by the ultimate goal of producing potent neutralizing monoclonal antibodies with optimal pharmacokinetic properties and low immunogenicity. This review then provides an outline of the most recent achievements in antivenom research, which include the application of new biotechnologies, the development of the first human monoclonal antibodies that can neutralize animal toxins, and efforts toward creating fully recombinant antivenoms. Lastly, future perspectives in the field of envenoming therapies are discussed, including rational engineering of antibody cross-reactivity and the use of oligoclonal antibody mixtures.
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spelling doaj.art-77f914eb29854ef6a75ebcce9e06455a2022-12-22T00:16:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-07-011010.3389/fimmu.2019.01598467484History of Envenoming Therapy and Current PerspectivesManuela B. Pucca0Manuela B. Pucca1Felipe A. Cerni2Felipe A. Cerni3Rahel Janke4Erick Bermúdez-Méndez5Line Ledsgaard6José E. Barbosa7Andreas H. Laustsen8Medical School, Federal University of Roraima, Boa Vista, BrazilDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BrazilDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkFacultad de Farmacia, Universidad de Costa Rica, San José, Costa RicaDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkDepartment of Biochemistry and Immunology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BrazilDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, DenmarkEach year, millions of humans fall victim to animal envenomings, which may either be deadly or cause permanent disability to the effected individuals. The Nobel Prize-winning discovery of serum therapy for the treatment of bacterial infections (tetanus and diphtheria) paved the way for the introduction of antivenom therapies for envenomings caused by venomous animals. These antivenoms are based on polyclonal antibodies derived from the plasma of hyperimmunized animals and remain the only specific treatment against animal envenomings. Following the initial development of serum therapy for snakebite envenoming by French scientists in 1894, other countries with high incidences of animal envenomings, including Brazil, Australia, South Africa, Costa Rica, and Mexico, started taking up antivenom production against local venomous animals over the course of the twentieth century. These undertakings revolutionized envenoming therapy and have saved innumerous patients worldwide during the last 100 years. This review describes in detail the above-mentioned historical events surrounding the discovery and the application of serum therapy for envenomings, as well as it provides an overview of important developments and scientific breakthroughs that were of importance for antibody-based therapies in general. This begins with discoveries concerning the characterization of antibodies, including the events leading up to the elucidation of the antibody structure. These discoveries further paved the way for other milestones in antibody-based therapies, such as the introduction of hybridoma technology in 1975. Hybridoma technology enabled the expression and isolation of monoclonal antibodies, which in turn formed the basis for the development of phage display technology and transgenic mice, which can be harnessed to directly obtain fully human monoclonal antibodies. These developments were driven by the ultimate goal of producing potent neutralizing monoclonal antibodies with optimal pharmacokinetic properties and low immunogenicity. This review then provides an outline of the most recent achievements in antivenom research, which include the application of new biotechnologies, the development of the first human monoclonal antibodies that can neutralize animal toxins, and efforts toward creating fully recombinant antivenoms. Lastly, future perspectives in the field of envenoming therapies are discussed, including rational engineering of antibody cross-reactivity and the use of oligoclonal antibody mixtures.https://www.frontiersin.org/article/10.3389/fimmu.2019.01598/fullenvenoming therapyantivenomantibodiesantiserumhybridoma technologyphage display
spellingShingle Manuela B. Pucca
Manuela B. Pucca
Felipe A. Cerni
Felipe A. Cerni
Rahel Janke
Erick Bermúdez-Méndez
Line Ledsgaard
José E. Barbosa
Andreas H. Laustsen
History of Envenoming Therapy and Current Perspectives
Frontiers in Immunology
envenoming therapy
antivenom
antibodies
antiserum
hybridoma technology
phage display
title History of Envenoming Therapy and Current Perspectives
title_full History of Envenoming Therapy and Current Perspectives
title_fullStr History of Envenoming Therapy and Current Perspectives
title_full_unstemmed History of Envenoming Therapy and Current Perspectives
title_short History of Envenoming Therapy and Current Perspectives
title_sort history of envenoming therapy and current perspectives
topic envenoming therapy
antivenom
antibodies
antiserum
hybridoma technology
phage display
url https://www.frontiersin.org/article/10.3389/fimmu.2019.01598/full
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