Project description
In-depth study of naturally acquired antibodies in pregnancy-associated malaria
Pregnancy-associated malaria or placental malaria (PM) is life-threatening to both the mother and the developing foetus. Prevention and treatment of malaria in prenatal care are essential in areas where the parasite is endemic. PM mainly affects first-time pregnant women, as immunity develops over successive pregnancies. This acquired protection is mediated by antibodies to parasite antigen VAR2CSA. Previous data has demonstrated that the naturally acquired response is cross-reactive, recognising multiple VAR2CSA variants. However, the recent trials of a VAR2CSA-based vaccine to prevent PM showed significant variant specificity of the induced antibodies. The EU-funded PAMSEQ research project aims to resolve that contradiction and investigate in detail the specificity and sequences of VAR2CSA antibodies generated in the course of natural infection.
Objective
Placental malaria (PM) is a severe malaria complication in pregnancy, in areas with stable parasite transmission. It is a major cause of disease and death among pregnant women and their offspring. PM mainly affects primigravidae, as immunity is developed over successive pregnancies. This naturally acquired protection to PM is mediated by antibodies targeting a parasite antigen called VAR2CSA. Although VAR2CSA is a variable antigen, it has been previously demonstrated that the naturally acquired antibody response is generally broadly cross-reactive (meaning that serum from a multigravidae woman can recognize multiple VAR2CSA variants). However, the results of recently conducted trials of a VAR2CSA-based vaccine to prevent PM showed almost complete variant-specificity of the induced antibodies (only the particular VAR2CSA variant used for immunization was recognized), failing at mimicking what occurs during natural infection. This research project aims to resolve that conundrum by studying in detail the specificity and sequence characteristics of VAR2CSA-specific antibodies generated during natural infection. Specifically, I will collect B cells from Ghanaian women with naturally acquired PM immunity. I will then identify B cells producing antibodies that can react with a panel of recombinant protein variants selected to represent the global variation in VAR2CSA. I will then use an innovative technology (LIBRA-seq) to simultaneously identify the exact antigen specificity of each single VAR2CSA-reactive B-cell and importantly the exact sequence of the antibody encoded by the cell. The latter information will allow me to produce recombinant antibodies to be tested for cross-reactivity towards recombinant and native VAR2CSA variants, and for their ability to neutralize the function of VAR2CSA. The project has major potential to accelerate development of VAR2CSA-specific vaccines against PM.
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 immunisation
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- medical and health sciences clinical medicine obstetrics
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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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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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.
1165 KOBENHAVN
Denmark
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.