Descripción del proyecto
Estudio en detalle de los anticuerpos adquiridos en la malaria asociada al embarazo
La malaria asociada al embarazo o infección placentaria por malaria es potencialmente mortal tanto para la madre como para el feto en desarrollo. La prevención y el tratamiento de la malaria en los cuidados prenatales son fundamentales en las zonas donde el parásito es endémico. La infección placentaria por malaria afecta sobre todo a mujeres primigestas, dado que la inmunidad se desarrolla a lo largo de los embarazos sucesivos. Este protección adquirida está mediada por anticuerpos frente al antígeno del parásito VAR2CSA. Los datos anteriores han demostrado que la respuesta adquirida de forma natural presenta reactividad cruzada, por lo que reconoce múltiples variantes de VAR2CSA. Sin embargo, las pruebas recientes de una vacuna basada en el VAR2CSA para evitar la infección placentaria por malaria mostraron una especificidad variante significativa de los anticuerpos inducidos. El proyecto PAMSEQ, financiado con fondos europeos, pretende resolver esa contradicción e investigar en detalle la especificidad y las secuencias de los anticuerpos VAR2CSA generados durante la infección natural.
Objetivo
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.
Ámbito científico
- 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
Palabras clave
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
1165 Kobenhavn
Dinamarca