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
- 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)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
1165 Kobenhavn
Denmark