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

• Grant number: 17/14035-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2018
• End date: March 31, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Eliane Candiani Arantes Braga
• Grantee: Felipe Augusto Cerni
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 18/14158-9 - Improving of human fragment antibodies (scFvs) specific for animals' venoms, BE.EP.PD

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 antivenoms. Although heterologous antivenoms are the only effective treatment available for severe envenoming, these sera present several documented undesirable problems: (i) Heterologous antivenoms can cause pyrogenic and anaphylactic reactions; (ii) Due to 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 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 fully human antibodies. The Laboratory of Molecular Immunopathology (LIM), under the responsibility of the physician and Dr. 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 fragment variable) human antibodies to scorpion venoms - Serrumab (Tityus serrulatus), jararaca venoms - Bothrumab (Bothrops sp), rattlesnakes venoms - Crotumab (Crotalus durissus terrificus), surucucu venoms - Lachesumab (Lachesis muta), coral venoms - Micrurumab (Micrurus leminiscatus), and Africanized bee venoms - Afribumab. However, although they are already patented and/or are under 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 functional in vitro and in vivo functional assays. (AU)

Scientific publications

(14)

(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)

BOLDRINI-FRANCA, JOHARA; PINHEIRO-JUNIOR, ERNESTO LOPES; PEIGNEUR, STEVE; PUCCA, MANUELA BERTO; CERNI, FELIPE AUGUSTO; BORGES, RAFAEL JUNQUEIRA; COSTA, TASSIA RAFAELLA; IMAI CARONE, SANTE EMMANUEL; DE MATTOS FONTES, MARCOS ROBERTO; SAMPAIO, SUELY VILELA; et al. Beyond hemostasis: a snake venom serine protease with potassium channel blocking and potential antitumor activities. SCIENTIFIC REPORTS, v. 10, n. 1, MAR 11 2020. (15/18432-0, 15/00740-0, 18/14158-9, 16/24191-8, 15/16714-8, 17/13485-3, 11/23236-4, 17/14035-1, 16/04761-4, 14/16182-3, 15/17286-0)

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)

OLIVEIRA, ISADORA S.; FERREIRA, ISABELA G.; ALEXANDRE-SILVA, GABRIEL M.; CERNI, FELIPE A.; CREMONEZ, CAROLINE M.; ARANTES, ELIANE C.; ZOTTICH, UMBERTO; PUCCA, MANUELA B.. Scorpion toxins targeting Kv1.3 channels: insights into immunosuppression. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 25, APR 15 2019. (18/21233-7, 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)

ALEXANDRE-SILVA, GABRIEL M.; BRITO-SOUZA, PABLO A.; OLIVEIRA, ANA C. S.; CERNI, FELIPE A.; ZOTTICH, UMBERTO; PUCCA, MANUELA B.. The hygiene hypothesis at a glance: Early exposures, immune mechanism and novel therapies. Acta Tropica, v. 188, p. 16-26, DEC 2018. (17/14035-1)

MANUELA B. PUCCA; MICHELLE V. S. FRANCO; JILVANDO M. MEDEIROS; ISADORA S. OLIVEIRA; SHIRIN AHMADI; FELIPE A. CERNI; UMBERTO ZOTTICH; BRUNA K. BASSOLI; WUELTON M. MONTEIRO; ANDREAS H. LAUSTSEN. Chronic kidney failure following lancehead bite envenoming: a clinical report from the Amazon region. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, 2020-12-14. (17/03580-9, 17/14035-1)

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)

PUCCA, MANUELA B.; BERNARDE, PAULO SERGIO; ROCHA, ANDERSON MACIEL; VIANA, PATRIK F.; FARIAS, RAIMUNDO ERASMO SOUZA; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; FERREIRA, ISABELA G.; SANDRI, ELISEU A.; SACHETT, JACQUELINE; et al. Crotalus Durissus Ruruima: Current Knowledge on Natural History, Medical Importance, and Clinical Toxinology. FRONTIERS IN IMMUNOLOGY, v. 12, p. 22-pg., 2021-06-08. (17/03580-9, 17/14035-1)

PUCCA, MANUELA B.; BERNARDE, PAULO SERGIO; ROCHA, ANDERSON MACIEL; VIANA, PATRIK F.; FARIAS, RAIMUNDO ERASMO SOUZA; CERNI, FELIPE A.; OLIVEIRA, ISADORA S.; FERREIRA, ISABELA G.; SANDRI, ELISEU A.; SACHETT, JACQUELINE; et al. rotalus Durissus Ruruima: Current Knowledge on Natural History, Medical Importance, and Clinical Toxinolog. FRONTIERS IN IMMUNOLOGY, v. 12, JUN 8 2021. (17/14035-1, 17/03580-9)

PUCCA, MANUELA B.; KNUDSEN, CECILIE; S. OLIVEIRA, ISADORA; RIMBAULT, CHARLOTTE; A. CERNI, FELIPE; WEN, FAN HUI; SACHETT, JACQUELINE; SARTIM, MARCO A.; LAUSTSEN, ANDREAS H.; MONTEIRO, WUELTON M.. Current Knowledge on Snake Dry Bites. TOXINS, v. 12, n. 11, NOV 2020. (17/14035-1, 17/03580-9)

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)

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)

MEDEIROS, JILVANDO M.; OLIVEIRA, ISADORA S.; FERREIRA, ISABELA G.; ALEXANDRE-SILVA, GABRIEL MELO; CERNI, FELIPE A.; ZOTTICH, UMBERTO; PUCCA, MANUELA B.. Fatal Rattlesnake Envenomation in Northernmost Brazilian Amazon: A Case Report and Literature Overview. REPORTS, v. 3, n. 2, p. 12-pg., 2020-06-01. (17/03580-9, 17/14035-1)