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B Cell Immunodominance in Antiviral Immunity

Project description

B-cell immunodominance and vaccination against viruses

Influenza A human virus causes many deaths every year. It is an enormous economic burden to society. Immunodominance represents an immunological phenomenon when immune responses are developed against only a few of the antigenic peptides out of the many available. The EU-funded B-DOMINANCE project aims to find out how B cell specificity and immunodominance define primary and secondary humoral responses to influenza virus. Previously, researchers generated a set of mutant viruses to study immunodominance and B cell interclonal competition in primary and secondary responses. This current study will use these mutants in combination with immunological methods, multi-colour flow cytometry, and single cell RNA and B cell receptor sequencing to gain fundamental knowledge on B cell regulation and anti-viral humoral responses.

Objective

This proposal aims at understanding how B cell specificity and immunodominance shape primary and secondary humoral responses to influenza A virus. Influenza A virus is a relevant human pathogen causing a considerable yearly death toll and economic burden to society. Immunodominance is a major driving force of adaptive immunity and defines the hierarchical recognition of epitopes on the same antigen. Previous studies analysing B cell dynamics in primary and secondary responses have been mainly focusing on simple antigens and competition between B cell clones of the same family. Investigation using complex antigens and examining interclonal competition are surprisingly scarce. Influenza hemagglutinin (HA) is a prime candidate to study immunodominance in B cells. I have generated a set of mutant viruses that will allow for an unprecedented investigation into immunodominance and B cell interclonal competition in primary and secondary responses. These viruses can be used to isolate and enumerate antibody and B cells specific for different epitopes on the same complex antigen (HA). I will use these unique tools in combination with state-of-the-art immunological methods, multi-colour flow cytometry and single cells RNA sequencing paired with B cell receptor sequencing to gain fundamental insights into B cell regulation and anti-viral humoral responses. I will i) study the link between B cell receptor characteristics, specificity and B cell fate decisions in primary responses, ii) characterize the relative contribution of pre-existing B cells, serum antibodies and CD4 T cells for immunodominance of secondary responses, iii) define immunodominance in human individuals, repeatedly exposed to influenza virus. I expect this project to critically improve our understanding of basic B cell biology with the long-term benefit of improving current vaccination against variable viral pathogens.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2019-STG

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Host institution

GOETEBORGS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 481 697,00
Address
VASAPARKEN
405 30 Goeteborg
Sweden

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Region
Södra Sverige Västsverige Västra Götalands län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 481 697,00

Beneficiaries (1)

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