Construction and selection of a library of scFv monoclonal antibodies against the SARS-CoV-2 spike protein by Phage Display technology

• Grant number: 22/05566-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2023
• Effective date (End): July 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Carlos Roberto Prudencio
• Grantee: Hernan Hermes Monteiro da Costa
• Host Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 21/11936-3 - Center for Translational Science and Biopharmaceutical Development, AP.CCD

Abstract

Antibodies against SAR-CoV-2 are essential for understanding and fighting the COVID-19 pandemic. They perform some functions, such as elimination of the virus from infected patients, reagents for rapid diagnoses, constitute the first line of treatment for hospitalized patients and are the main objective of vaccine development. The vaccines and therapeutic antibodies currently available were developed from the spike protein of SARS-CoV-2 variants that circulated during the first phases of the Pandemic in 2020. The emergence of new variants, from mutations in the receptor binding site (RBD) of the spike protein, has raised concerns about the impairment of neutralizing antibody responses and the effectiveness of vaccination programs. In this context, the objective of this proposal is the generation of monoclonal antibodies against the spike protein of the Brazilian variant P.1 for immunotherapy and prevention of COVID-19. Antibodies will be selected against the spike protein from a library of scFv antibody fragments using Phage display technology. After selection, the most reactive antibodies will be produced in the scFv-Fc format in mammalian cells, and later, the functional characterization of these antibodies will be carried out, such as the analysis of the neutralizing potential of the antibodies in relation to the virus and also in silico analysis for characterization of the antigen-antibody interaction. It is expected that this study will be able to provide a bank of neutralizing antibodies to the SARS-CoV-2 virus that can contribute to the development of effective immunotherapies in the clinical management of patients with COVID-19 in the near future.