Discovery of human monoclonal antibodies (scFv) with cross-reactivity and pH-dependent targeting metalloprotease from Bothrops spp.

• Grant number: 22/08964-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: January 02, 2023
• End date: December 02, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Eliane Candiani Arantes Braga
• Grantee: Isadora Sousa de Oliveira
• Supervisor: Andreas Hougaard Laustsen
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Technical University of Denmark (DTU), Denmark
• Associated to the scholarship: 20/13176-3 - Human monoclonal antibodies (scFv) discovery with cross-reactivity and pH-dependent to metalloproteases from Bothrops spp, BP.PD

Abstract

Snakebite accidents affect more than 5 million people worldwide per year, which results in more than 100,000 deaths and around 300,000 amputations or other permanent disabilities, being classified as category A of Neglected Tropical Diseases (NTDs) list in 2017. In Brazil, these accidents are mostly caused by snakes from Bothrops genus, which is distributed throughout the territory. Its venom is mainly composed of metalloproteases (~30-70%), varying quantitatively between species, and the venom is known to be hemorrhagic, proteolytic and coagulant, responsible for many of their local and systemic manifestations. The treatment for these envenomings is the administration of heterologous antivenom. However, there are still several disadvantages regarding its use, since they can trigger hypersensitivity reactions, such as anaphylaxis and Serum Disease. Thus, new technologies for antivenom production have become essential for the antivenoms improvement, such as the phage display technique, which allows the selection of fully human antibodies against the most varied antigens. Previously studies with Bothrops snakes demonstrated only human monoclonal antibodies specific for PLA2 produced using this technique. This research project seeks the selection and production of human monoclonal antibodies of single-chain fragment variable (scFvs) type, through the phage display technique, capable of recognizing and neutralizing metalloproteases from botropic venoms. The project will also produce improved antibodies, that is, they should be pH-depending and cross-reactive for metalloproteases of different botropic species, constituting a new generation antibotropic serum. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SALIMO, ZECA M.; BARROS, ANDRE L.; ADRIAO, ASENATE A. X.; RODRIGUES, ALINE M.; SARTIM, MARCO A.; DE OLIVEIRA, ISADORA S.; PUCCA, MANUELA B.; BAIA-DA-SILVA, DJANE C.; MONTEIRO, WUELTON M.; DE MELO, GISELY C.; et al. Toxins from Animal Venoms as a Potential Source of Antimalarials: A Comprehensive Review. TOXINS, v. 15, n. 6, p. 26-pg., 2023-06-01. (20/13176-3, 22/08964-8)

GALAN, LUIS E. B.; SILVA, VITORIA SOUZA; SILVA, VITORIA SANTOS; MONTE, ROMMEL C. C.; JATI, SEWBERT R. R.; OLIVEIRA, ISADORA S. S.; CERNI, FELIPE A. A.; MONTEIRO, WUELTON M. M.; SACHETT, JACQUELINE; DANTAS, DOMINGOS S. M.; et al. Acute mesenteric ischemia following lancehead snakebite: an unusual case report in the Northernmost Brazilian Amazon. FRONTIERS IN MEDICINE, v. 10, p. 7-pg., 2023-06-22. (20/13176-3, 22/08964-8)

CARVALHO, ERICA S.; OLIVEIRA, ISADORA; NASCIMENTO, THAIS P.; NETO, ALEXANDRE VILHENA DA SILVA; LEAL, BRENDA A. S.; ARAUJO, FELIPE Q.; JULIAO, BRUNO F. V.; SOUZA, ANDREA R. N.; ABRAHIM, ANDREZA W.; MACEDO, BRUNA B. O.; et al. Prospecting Local Treatments Used in Conjunction with Antivenom Administration Following Envenomation Caused by Animals: A Systematic Review. TOXINS, v. 15, n. 5, p. 19-pg., 2023-04-28. (20/13176-3, 22/08964-8)

ISADORA SOUSA DE OLIVEIRA; NICOLY MALACHIZE ALANO-DA-SILVA; ISABELA GOBBO FERREIRA; FELIPE AUGUSTO CERNI; JACQUELINE DE ALMEIDA GONÇALVES SACHETT; WUELTON MARCELO MONTEIRO; MANUELA BERTO PUCCA; ELIANE CANDIANI ARANTES. Understanding the complexity of Tityus serrulatus venom: A focus on high molecular weight components. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 30, 2024-01-22. (22/08964-8, 20/13176-3, 21/11547-7, 21/11936-3, 19/10173-6)

GABRIELA DE OLIVEIRA ALMEIDA; ISADORA SOUSA DE OLIVEIRA; ELIANE CANDIANI ARANTES; SUELY VILELA SAMPAIO. Snake venom disintegrins update: insights about new findings. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 29, 2023-09-18. (22/05554-3, 22/08964-8, 20/13176-3, 19/10173-6, 20/15670-5, 21/11936-3, 22/04804-6)