Phage-display panning to screen neutralizing anti-scorpionic and anti-TIM-3 VHHs

• Grant number: 23/07845-8
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Start date: March 11, 2024
• End date: June 10, 2024
• Field of knowledge: Agronomical Sciences - Veterinary Medicine
• Principal Investigator: Débora Botéquio Moretti
• Grantee: Débora Botéquio Moretti
• Visiting researcher: Gladys Viviana Parreño
• Visiting researcher institution: Instituto Nacional de Tecnología Agropecuaria (INTA) , Argentina
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil
• City of the host institution: São Paulo

Abstract

Nanobodies (Nbs or VHHs) have great therapeutic potential and have been studied as a treatment for numerous diseases. In addition to being more cost-effective to produce, these camelid-derived single-domain antibody fragments are small, stable, soluble in aqueous solutions, and have high specificity and affinity for the target antigen. Furthermore, VHHs exhibit low toxicity and immunogenicity due to their small size, identity with the human heavy chain region, and rapid renal clearance. These characteristics and the ability to adapt nanobodies for in vivo applications make these molecules a promising and innovative generation of therapeutic proteins. The use of this technology is poor explored in Brazil. In this sense, the Instituto Butantan established in 2021 a partnership with the National Institute of Agricultural Technology (INTA/Argentina) for the co-development of nanobodies against scorpion toxin. In 2022, the development of nanobodies against the TIM-3 protein was added to this proposal. Thus, the institutions agreed to carry out a work plan that involves immunizing llamas and obtaining immune libraries by INTA and obtaining and characterizing VHHs by INTA and Instituto Butantan. Thus, the present work plan for the visiting researcher Dra Gladys Viviana Parreño (INTA/Argentina) aims to carry out the "Panning of Antigen-Specific Nanobodies" together with the institute's researchers. Using the technique, antigen-specific clones containing desired nanobodies will be selected from an immune library obtained by immunizing llamas with scorpion antigen and TIM-3 protein. The development of the activity plan will be important to bring to the Instituto Butantan a new technological platform for the production of recombinant nanobodies and to establish a solid cooperation between INTA/Argentina and Instituto Butantan/Brazil, strengthening the partnership between Latin American institutions. (AU)