Project description
How B cells respond during helminth infections
A quarter of the world’s population is infected by parasitic worms (helminths), which can affect immune responses to vaccines and infections. While we know these worms can weaken the immune system, it’s not certain how they affect the generation of protective antibodies by B cells. The ERC-funded B-SELECT project aims to discover how specific B cells are formed and how helminths impair their development. Conducting studies at the molecular level, the project will determine how B cells are activated and selected during helminth infections. The findings are expected to shed light on how we can bypass the interference caused by helminths and help scientists design more effective vaccines.
Objective
One-fourth of the global population is currently infected with helminths, which modulate host immunity against not only their own antigens but also non-cognate antigens, including vaccines. While antigen-specific antibodies and memory B cells are essential for protection against infectious diseases, how the B cell response quality is influenced by helminths remains largely unknown. With my core expertise in studying responses to parasites at the level of single B cells and monoclonal antibodies, I aim to delineate the onset and quality of B cell responses formed during immunoregulatory helminth infections, impacting the development of effective vaccines.
The B cell response quality relies on recruiting antigen-specific naïve cells and selecting high-affinity B cells to form antibody-secreting cells and memory B cells. However, how these well-established mechanisms are impaired during B cell immunity modulated by helminths remains unknown. Therefore, the goal of this ERC proposal is to elucidate the molecular principles governing the formation and selection of antigen-specific B cells during helminth-induced immunoregulation and to identify strategies to mitigate modulation.
To achieve this, I will investigate the origin and development of de novo helminth antigen-specific B cell responses in the unique controlled helminth infections in naïve individuals and vaccine-specific B cell responses in residents of helminth-endemic areas. Access to clinical samples, advanced human tonsil organoids and transgenic mouse models, combined with my state-of-the-art expertise in studying antigen-specific B cells, uniquely positions me to uncover paradigm-shifting molecular principles that guide B cell responses during helminth infections. Ultimately, I aim to provide the first proof of concept to mitigate modulatory effects and rescue B cell response quality, paving the way to address global health challenges by inducing protective vaccine response in helminth-infected individuals.
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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.
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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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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2025-STG
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2333 ZA Leiden
Netherlands
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