Characterization of the Antibody Repertoire of Workers at an Influenza A Vaccine Factory

• Grant number: 24/04194-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2024
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Esper Georges Kallás
• Grantee: Anne Karoline Rocha Medrado Ventura
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/07040-1 - Center of Research and Development in Immunobiologicals, AP.NPOP

Abstract

Influenza viruses are capable of infecting humans and animals, are widely distributed and can cause seasonal epidemics associated with highly contagious respiratory infections that can be caused by more than one type of influenza virus, with the most prevalent infections caused by the influenza A virus (IAV). IAVs represent a very diverse group due to the antigenic variations associated with surface glycoproteins, which play an essential role in virulence and viral pathogenesis, in addition to being the main antigenic targets of protective antibodies induced during natural infection or after vaccination. To prevent the entry of the virus into the cell, the presence of an efficient neutralizing antibody is essential. In view of this, the production of a monoclonal antibody (mAb), which includes different epitopes from different strains of IAV, is a very important gap to be filled in the literature. The characterization of the B cell response and antibodies directed to influenza viruses derived from these cells is extremely important for understanding and selecting the best candidate mAb. Therefore, the aim of this study is to identify possible broad-spectrum neutralizing antibodies in individuals frequently exposed to different strains of IAV. For this, immunophenotyping will be performed to characterize and evaluate the kinetics of B cell subpopulations for different virus subtypes with the aid of influenza-specific probes. Next, a cell isolation approach will be used to characterize possible sequences of neutralizing antibodies and future production of broad-spectrum mAbs. Samples of peripheral blood mononuclear cells from workers at the Instituto Butantan influenza vaccine factory will be used, individuals frequently exposed to different strains of IAV, thus increasing the chance of finding a possible neutralizing antibody with potential for cross-reactivity. Studies in the area of therapeutic monoclonal antibodies (mAbs) have shown us that selected human IgG isotypes, natural and manipulated, have great potential for clinical application, both in prevention and treatment, and we hope to contribute even more to this purpose.