Objective
Malaria was the strongest selective pressure in recent human evolution, yet its profound impact on our immune system is poorly understood. My recent work showed that high autoantibody (AAb) titers correlate with a 41% reduced risk of febrile malaria. These AAbs inhibit Plasmodium falciparum (Pf) growth and bind Pf invasion proteins. I propose that effective malaria immunity is autoreactive, presenting a paradigm shift where controlled breakdowns in immune tolerance are essential for protection. As tolerance mechanisms limit autoreactive immunity, this may explain the slow acquisition of natural immunity and poor malaria vaccine efficacy. It was suggested that genetic susceptibility to autoimmunity evolved as a survival advantage against malaria, and my data indicate the ability to develop an AAb response was central to this adaptation. Despite genetic susceptibility and elevated AAb titers, individuals in malaria-endemic regions are relatively protected from autoimmune diseases, likely due to an immune environment driven by chronic Pf malaria and other pathogens.
Foundational knowledge, which is now technically within reach, is required to exploit the connection between autoimmune disease and infection immunity, to improve malaria vaccines and transform autoimmune therapies. I propose comparative studies of autoreactive B cells and antibodies in autoimmune disease patients and malaria-exposed individuals, using field studies in Africa and advanced antigen-specific B cell methods, together with mouse models, to address the following key questions: 1) Do immune tolerance mechanisms impair malaria immunity? 2) What defines the immune environment of chronic Pf exposure that protects from autoimmune diseases?
This research will illuminate the genetic and individual imprint shaped by malaria, reveal barriers to effective malaria immunity and uncover immunoregulatory mechanisms in chronic malaria, potentially identifying therapeutic strategies for inflammatory conditions.
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.
- medical and health sciences health sciences infectious diseases malaria
- medical and health sciences basic medicine immunology autoimmune diseases
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
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Keywords
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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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-COG
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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.
20359 Hamburg
Germany
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