Description du projet
Étude approfondie des anticorps naturellement acquis dans le paludisme placentaire
Le paludisme placentaire (PP) est une maladie potentiellement mortelle pour la mère et le fœtus en développement. La prévention et le traitement du paludisme dans le cadre des soins prénatals sont essentiels dans les régions où le parasite est endémique. Le PP touche principalement les femmes enceintes pour la première fois, l’immunité se développant au fil des grossesses successives. Cette protection acquise est assurée par des anticorps dirigés contre l’antigène parasitaire VAR2CSA. Des données antérieures ont démontré que la réponse naturellement acquise est à réaction croisée, avec une reconnaissance de multiples variantes de VAR2CSA. Cependant, les récents essais d’un vaccin à base de VAR2CSA pour prévenir le PP ont montré une spécificité variante significative des anticorps induits. Le projet de recherche PAMSEQ, financé par l’UE, vise à résoudre cette contradiction et à étudier en détail la spécificité et les séquences des anticorps VAR2CSA générés au cours d’une infection naturelle.
Objectif
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.
Champ scientifique
- medical and health scienceshealth sciencesinfectious diseasesmalaria
- medical and health sciencesbasic medicineimmunologyimmunisation
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- medical and health sciencesclinical medicineobstetrics
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
1165 Kobenhavn
Danemark