Postdoctoral Position in Immunology: Harnessing a Human Lymphoid Organ-on-chip for Evaluating Innovative mRNA Vaccination Strategies

Institut Pasteur

Paris, France

A post-doctoral position is available to advance the development of a 3D human lymphoid organ model and apply this model to test new mRNA vaccination platforms. The position is fully funded for 2.5 years in the frame of the European Vaccine Hub project.

Vaccine development is still hampered by the challenges of evaluating the immunogenicity of multiple vaccine candidates in humans. This issue can be addressed by harnessing advances in tissue engineering, via the design of new organ-on-chip models that mimic features and functions of human lymphoid tissues in vitro. In this project, we will take advantage of a recently developed lymphoid organ-on-chip model (LO chip; R. Jeger-Madiot et al., J Exp Med 2024) to assess novel mRNA vaccination strategies.

We will first aim at comparing the immune responses induced in the LO chip by classical mRNA-liponanoparticles (LNPs), self-amplifying mRNA LNPs, and mRNA-LNPs encoding self-assembling virus-like particles. The kinetics of antigen expression, the innate responses induced in antigen presenting cells, and the differentiation of specific B and T cells will be evaluated by spectral flow cytometry and scRNAseq, while CD4+ T cell/B cell interactions will be probed by confocal microscopy.

The project will then aim at devising a new generation LO chip model that better recapitulates the human lymphoid tissue architecture. We will use engineered stromal cells to generate tissue compartmentalization, aiming at recapitulating a T cell zone dedicated to DC/T cell interactions and a B cell zone where germinal center-like structures may develop. In first intent, T cell zones will be established using autologous stromal cells expressing FLT3L and CCL21, while B cell zones will be generated with stromal cells expressing CXCL13. The impact of spatial organization on vaccine responses will be assessed using the optimal mRNA-LNP formulation defined in Aim 1, with readouts focusing on specific B cell responses and antibody maturation. This project should provide a robust human-relevant platform for evaluating a broad variety of vaccination and immunotherapeutic strategies.

Qualifications:

We are looking for a skilled and highly motivated candidate with:

• a PhD in immunology, with expertise in T cell/B cell interactions and/or vaccinology;
• an expertise in advanced flow cytometry;
• a strong motivation to learn organ-on-chip technologies;
• a track record of publications in relevant scientific fields.

Expertise in tissue engineering will be an asset. Good communication skills in spoken and written English are essential.