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History of Envenoming Therapy and Current Perspectives

Texto completo
Pucca, Manuela B. [1, 2] ; Cerni, Felipe A. [1, 3] ; Janke, Rahel [1] ; Bermudez-Mendez, Erick [4] ; Ledsgaard, Line [1] ; Barbosa, Jose E. [3] ; Laustsen, Andreas H. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Tech Univ Denmark, Dept Biotechnol & Biomed, Lyngby - Denmark
[2] Univ Fed Roraima, Sch Med, Boa Vista - Brazil
[3] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Biochem & Immunol, Ribeirao Preto - Brazil
[4] Univ Costa Rica, Fac Farm, San Jose - Costa Rica
Número total de Afiliações: 4
Tipo de documento: Artigo de Revisão
Fonte: FRONTIERS IN IMMUNOLOGY; v. 10, JUL 10 2019.
Citações Web of Science: 1

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. (AU)

Processo FAPESP: 17/04724-4 - Melhoramento de fragmentos de anticorpos humanos (scFVs) específicos para peçonhas animais
Beneficiário:Eliane Candiani Arantes Braga
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/14035-1 - Melhoramento de fragmentos de anticorpos humanos (scFVs) específicos para peçonhas animais
Beneficiário:Felipe Augusto Cerni
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 18/14158-9 - Melhoramento de fragmentos de anticorpos humanos (scFvs) específicos para peçonhas animais
Beneficiário:Felipe Augusto Cerni
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado