Improving of human fragment antibodies (scFVs) specific for animals' venoms

• Grant number: 17/04724-4
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2017
• End date: September 30, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eliane Candiani Arantes Braga
• Grantee: Eliane Candiani Arantes Braga
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Andreas Hougaard Laustsen ; Iara Aimê Cardoso ; Karla de Castro Figueiredo Bordon ; Manuela Berto Pucca
• Associated scholarship(s): 18/03923-6 - Improving of human fragment antibodies (scFvs) specific for animals' venoms, BP.TT

Abstract

Accidents caused by venomous animals are classified as Neglected Tropical Diseases (NTDs). Currently, the specific treatment available for severe envenoming caused by venomous animals is the use of heterologous antivenons. Although heterologous antivenoms are currently the only effective treatment available for severe envenoming, these sera present several documented undesirable problems: (i) Heterologous antivenoms may cause pyrogenic and anaphylactic reactions; (ii) Because of their heterologous nature, horse antibodies present in sera can act as antigens and activate the human immune system, resulting in the production of human anti-horse antibody antibodies; (iii) Most of these antibodies (70%) are not targeted to clinically relevant toxins, but directed against other exogenous antigens that the immunized animal encountered during its lifetime; (iv) Large numbers of heterologous antibodies combined with human anti-horse antibody antibodies can result in high production of immunocomplexes, triggering Serum Sickness. Thus, in order to avoid all such problems, the most desirable alternative would be the production of homologous, that is, fully human antibodies. The Laboratory of Molecular Immunopathology (LIM), under the responsibility of the physician and PhD José Elpidio Barbosa, has been dedicating more than a decade to the production of antivenoms consisting of fragments of human antibodies. Using Phage Display technology, the present laboratory produced scFv (single-chain fragmente variable) human antibodies to scorpion venoms - Serrumab (Tityus serrulatus), jararaca - Bothrumab (Bothrops sp), rattlesnake - Crotumab (Crotalus durissus terrificus), surucucu - Lachesumab (Lachesis muta), coral - Micrurumab (Micrurus leminiscatus) and Africanized bee - Afribumab. Today, the group represents 30% of the world's publications in the area. However, although they are already patented and / or in the process of patenting, many of them need to be improved on their affinity and format before being included in a mixture of antivenoms, aiming at a future transfer of technology and availability in the pharmaceutical market. In this context, the present project will seek to improve affinity and optimize the format of Serrumab and Afribumab antibodies. Subsequently, the improved antibodies will be used in in vitro and in vivo functional assays. (AU)

Scientific publications

(6)

(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)

ABREU, CAIO B.; BORDON, KARLA C. F.; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; BALENZUELA, CARLA; ALEXANDRE-SILVA, GABRIEL M.; ZOCCAL, KARINA F.; REIS, MOUZARLLEM B.; WIEZEL, GISELE A.; PEIGNEUR, STEVE; et al. Pioneering Study onRhopalurus crassicaudaScorpion Venom: Isolation and Characterization of the Major Toxin and Hyaluronidase. FRONTIERS IN IMMUNOLOGY, v. 11, AUG 20 2020. (17/00586-6, 16/04761-4, 17/04724-4, 17/03580-9, 19/10173-6, 17/14035-1, 18/21233-7)

PUCCA, MANUELA B.; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; JENKINS, TIMOTHY P.; ARGEMI, LIDIA; SORENSEN, CHRISTOFFER V.; AHMADI, SHIRIN; BARBOSA, JOSE E.; LAUSTSEN, ANDREAS H.. Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy. FRONTIERS IN IMMUNOLOGY, v. 10, SEP 6 2019. (18/14158-9, 18/21233-7, 17/04724-4, 17/14035-1, 17/03580-9)

FIGUEIREDO BORDON, KARLA DE CASTRO; COLOGNA, CAMILA TAKENO; FORNARI-BALDO, ELISA CORREA; PINHEIRO-JUNIOR, ERNESTO LOPES; CERNI, FELIPE AUGUSTO; AMORIM, FERNANDA GOBBI; PINO ANJOLETTE, FERNANDO ANTONIO; CORDEIRO, FRANCIELLE ALMEIDA; WIEZEL, GISELE ADRIANO; CARDOSO, IARA AIME; et al. From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery. FRONTIERS IN PHARMACOLOGY, v. 11, JUL 24 2020. (17/14035-1, 17/00586-6, 18/14158-9, 19/10173-6, 18/21233-7, 17/04724-4, 13/26619-7, 16/04761-4, 17/03580-9, 13/26200-6)

CAMPOS, LUCAS B.; PUCCA, MANUELA B.; SILVA, LUCIANO C.; PESSENDA, GABRIELA; FILARDI, BRUNO A.; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; LAUSTSEN, ANDREAS H.; ARANTES, ELIANE C.; BARBOSA, JOSE E.. Identification of cross-reactive human single-chain variable fragments against phospholipases A(2) from Lachesis muta and Bothrops spp venoms. Toxicon, v. 184, p. 116-121, SEP 2020. (17/04724-4, 17/14035-1, 18/14158-9, 17/03580-9)

PUCCA, MANUELA B.; CERNI, FELIPE A.; JANKE, RAHEL; BERMUDEZ-MENDEZ, ERICK; LEDSGAARD, LINE; BARBOSA, JOSE E.; LAUSTSEN, ANDREAS H.. History of Envenoming Therapy and Current Perspectives. FRONTIERS IN IMMUNOLOGY, v. 10, JUL 10 2019. (17/14035-1, 18/14158-9, 17/04724-4)

PUCCA, MANUELA B.; AHMADI, SHIRIN; CERNI, FELIPE A.; LEDSGAARD, LINE; SORENSEN, V, CHRISTOFFER; MCGEOGHAN, FARRELL T. S.; STEWART, TRENTON; SCHOOF, ERWIN; LOMONTE, BRUNO; KELLER, ULRICH AUF DEM; et al. Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins. FRONTIERS IN PHARMACOLOGY, v. 11, MAY 7 2020. (17/04724-4, 17/14035-1, 18/14158-9)