Outlining the Role of IgA in Memory Instruction
The ORIgAMI project aims to investigate the role of IgA+ B cells in respiratory infections to enhance vaccine design against airborne viruses like influenza and SARS-CoV-2.
Projectdetails
Introduction
Several times in human history, we faced sudden outbreaks of respiratory viruses that rapidly spread over the world before we could design broadly protective vaccines. Such was the case of the H1N1 influenza virus that killed 50 million people during the 1918 Spanish flu and SARS-CoV-2 that led to at least 5 million deaths during the current COVID-19 pandemic.
Immune Response
Influenza and SARS-CoV-2 elicit robust humoral immune responses, including the production of virus-specific antibodies of the IgM, IgG, and IgA types. In particular, IgA plays a crucial role in protecting lung mucosal surfaces by neutralizing respiratory viruses and impeding their attachment to epithelial cells.
Current Vaccine Limitations
Despite its protective role, current vaccines against influenza and SARS-CoV-2 fail to produce significant levels of IgA in the respiratory tract. Therefore, a deeper understanding of the biology of IgA+ cells during respiratory infection is of utmost interest.
Research Focus
ORIgAMI is based on recent unexpected findings from my team showing that germinal center B cells expressing IgA are mostly recruited towards the long-lived plasma cell compartment rather than to the memory B cell one upon influenza infection. In this frame, we will determine if the IgA BCR biases cell fate by:
- Imprinting germinal center B cells with specific transcriptional/epigenetic programs.
- Favoring antigen extraction and recruitment of T cell help within germinal centers.
- Enhancing downstream B cell signaling pathways.
Methodology
To this end, we will use the influenza H1N1 virus as a respiratory infection model combined with a series of complementary innovative tools and methodologies:
- De novo-generated transgenic mice
- Single-cell RNA/ATAC-seq
- 3D imaging
- DNA-based force sensors
- Phospho- and imaging-flow cytometry
- Mass-spectrometry
Conclusion
A deep understanding of the biology of IgA+ B cells during respiratory viral infection is of fundamental interest and may provide clues towards the design of future vaccination approaches against airborne pathogens.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 2.049.049 |
Totale projectbegroting | € 2.049.049 |
Tijdlijn
Startdatum | 1-9-2023 |
Einddatum | 31-8-2028 |
Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALEpenvoerder
Land(en)
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This project aims to characterize mucosal IgA proteoforms to enhance vaccine and monoclonal antibody development for improved respiratory immunity against viral threats.
Investigating Virus-Host Interplay in Human Primary Models of Genetically Modified Respiratory Epithelium
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Deciphering the antibody-microbiota axis in early life
This project aims to explore how early life immune exposures shape immunoglobulin repertoires and their impact on health, particularly allergies, by analyzing B cell receptor sequences and microbiota antigens.
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This project aims to develop a diagnostic assay to predict influenza vaccine responsiveness in immunocompromised patients using identified biomarkers and machine learning models, enhancing personalized vaccination strategies.
Tracing virus-specific CD8+ T cell clonotype zonation and function in humans
This project aims to redefine the role and distribution of CD8+ T cells in viral immunity using single-cell technologies, focusing on their function against SARS-CoV-2 and informing future vaccine development.