Project description
The role of IgA+ B cells during respiratory viral infections
Respiratory viruses (H1N1 and SARS-CoV-2) spread quickly and can be deadly. They trigger IgA antibodies for lung protection, but vaccines do not produce enough IgA. After influenza infection, IgA B cells mostly become long-lived plasma cells instead of memory B cells. The ERC-funded ORIgAMI project aims to explore how the IgA B cell receptor (BCR) affects germinal centre B cells through specific transcriptional and epigenetic programmes. The findings can help improve antigen extraction, T cell recruitment, and B cell signalling. Using the influenza H1N1 virus as a model, the project will use transgenic mice, single-cell RNA and ATAC sequencing, and mass spectrometry. Understanding IgA+ B cells during respiratory viral infections could lead to new vaccination strategies.
Objective
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 pandemics. Influenza and SARS-CoV-2 elicit robust humoral immune responses, including 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. Despite its protective role, current vaccines against influenza and SARS-CoV-2 fail to produce significant levels of IgA in the respiratory tract. Then, a deeper understanding of the biology of IgA+ cells during respiratory infection is of utmost interest. 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:
1-Imprinting germinal center B cells with specific transcriptional/epigenetic programs.
2-Favoring antigen extraction and recruitment of T cell help within germinal centers.
3-Enhancing downstream B cell signalling pathways.
To to this end, we will use influenza H1N1 virus as 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, and mass-spectrometry. 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 air-borne pathogens.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- medical and health sciences health sciences public health epidemiology pandemics
- medical and health sciences health sciences infectious diseases viral diseases RNA viruses influenza
- medical and health sciences health sciences infectious diseases viral diseases RNA viruses coronaviruses
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2022-STG
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75654 Paris
France
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