Développement d'un vaccin à ARN messager contre le paludisme gestationnel / Development of a mR[...]

Organisation/Company: Sorbonne Université SIS (Sciences, Ingénierie, Santé)Country: FranceApplication Deadline: 4 Jun 2026 – 22:00 (UTC)Type of Contract: Temporary JobStatus: Full‑time

Offer Description

The most severe forms of malaria are caused by the parasite Plasmodium falciparum. Its virulence is associated with infected erythrocytes (IEs) sequestration from blood circulation by binding to endothelial cell surface receptors within microvessels of various tissues. Adhesion of IEs is mediated by members of the highly polymorphic and clonally variant P. falciparum erythrocyte membrane protein 1 (PfEMP1) exported to the IE surface. While the intracellular acidic terminal segment (ATS) is conserved, the extracellular region contains an N‑terminal segment (NTS) followed by multiple highly polymorphic Duffy‑binding‑like (DBL) domains and a cysteine‑rich inter‑domain region (CIDR), also termed ID. Specific antibodies to PfEMP1 are crucial for clinical immunity in malaria endemic areas.

Placental malaria (PM) is the best proof of concept that clinical immunity correlates to neutralizing antibodies targeting a specific PfEMP1. PM is characterized by a massive accumulation of IEs and monocytes in the placental intervillous blood spaces, causing adverse birth outcomes, notably low birth weight and increased perinatal and maternal mortality. Chondroitin sulfate A (CSA) is the primary receptor for IE sequestration in the placenta, and VAR2CSA is the PfEMP1 family member responsible for IE cytoadhesion to CSA. Antibodies targeting VAR2CSA and inhibiting the interaction with CSA have been correlated with PM protection. Therefore, VAR2CSA is the leading vaccine candidate to protect pregnant women against PM.

We have recently reported the safety and immunogenicity of a VAR2CSA‑derived PM vaccine (PRIMVAC) spanning the CSA‑binding DBL1x‑2x domain of the 3D7‑VAR2CSA variant in a Phase Ia/Ib clinical trial (ClinicalTrials.gov, NCT ). The vaccine was safe and induced antibodies that reacted with and inhibited CSA binding of the homologous strain, although limited cross‑reactivity with other VAR2CSA variants was observed.

The Severe Malaria Pathogenesis team is working on vaccine and immunotherapy approaches to protect against placental malaria. We aim to develop an experimental mRNA‑based placental malaria vaccine candidate capable of inducing high levels of antibodies that recognize multiple VAR2CSA variants and inhibit IE adhesion to CSA.

Responsibilities

The PhD student will:

• Design and characterize the humoral immune response in rats/mice vaccinated with various Placental Malaria mRNA vaccine candidates combined with different lipid nanoparticle (LNP) formulations.
• Identify the best mRNA vaccine candidate and combine it with other mRNA vaccines targeting the blood stage and/or the preerythrocytic stage of the parasite.
• Employ molecular biology, biochemistry, and immunology techniques to assess the generated humoral immune response in vaccinated animals.

Desired Technical Skills

• Molecular Biology : Proficiency in cloning techniques, PCR, RT‑qPCR, sequencing, and handling of expression vectors (e.g., plasmids, RNA).
• Biochemistry : Experience in protein purification, Western blot, ELISA, and antibody characterization techniques (e.g., titration, neutralization assays).
• Immunology : Knowledge of techniques for evaluating humoral immune responses (e.g., antibody assays, binding and inhibition tests, flow cytometry).
• Animal Models : Experience with murine or rodent models (mice/rats) for vaccine studies, including immunization, sample collection, and analysis of immune responses.

Additional Information

• “Début de la thèse”: 01/10/2026• “Funding category”: Contrat doctoral• “Concours pour un contrat doctoral - SU”

Work Location

Number of offers available: 1Company/Institute: Sorbonne Université SIS (Sciences, Ingénierie, Santé)Country: FranceCity: ParisGeofield