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© NIAID - CC by 2.0
Based on 'Human Natural Killer Cell' and 'Human B lymphocyte' from NIAID
Scientific Fields
Diseases
Organisms
Applications
Technique
Application Deadline
31
Jul 2025
2025-07-31 8:00:00 2025-07-31 18:00:00 Europe/Paris M2 internship in vaccines and immunology Addressing the mechanism of T cell activation after mRNA-based vaccination against influenza virus. TeamA M2 internship position is available in the Guermonprez lab at Institut Pasteur Paris (“Dendritic cells and adaptive immunity” Unit, Immunology […] "25-28 rue du Dr. Roux, 75015, Paris"

Addressing the mechanism of T cell activation after mRNA-based vaccination

against influenza virus.

Team
A M2 internship position is available in the Guermonprez lab at Institut Pasteur Paris (“Dendritic cells and adaptive immunity” Unit, Immunology Department https://research.pasteur.fr/fr/department/immunology/) in collaboration with the Group of Ignacio Garcia Verdugo at Institut Cochin (https://institutcochin.fr/).

Project
mRNA vaccines offer a unique and versatile technological platform enabling vaccination against emerging pathogens. Despite major successes in SARS-CoV2 vaccination, mRNA vaccines elicit CD8+ T cell responses that are less potent and long-lasting than other non-replicative viruses for instance. Also, the mechanisms underlying the activation of T cell responses against mRNA vaccines remain poorly understood. Lastly, the translation of mRNA vaccination from intra-muscular vaccination to mucosal vaccination remains an unmet technological need. In this context, induction of long lasting CD8 and CD4 memory T cells endowed with long lasting residency in the upper respiratory tract remain a highly pursued objective in vaccination against airborne viruses. Dendritic cells (DCs) are the sentinel of the immune system. DCs are developmentally and functionally heterogeneous and encompass multiple subsets including XCR1+IRF8+ DCs, and a variety of IRF4+ DCs (DC2As, DC2Bs, DC3s) and plasmacytoid DCs (pDCs and pDCs-like).

The general objectives of this project are:

  1. To determine the functional contribution of DCs subsets to T and B cell responses induced by mRNA vaccine;
  2. To explore novel avenues to increase the function of relevant DCs subsets to increase the formation of tissue, resident, long lasting memory T cell responses.

This project will be developed in the context of an influenza vaccine developed in the laboratory using B (HA) and conserved T cell epitopes (NP) from H1N1/PR8 influenza strain. This vaccine provides homologous and some level of heterologous protection.

Mission

The specific objectives of the M2 are:
1°) To identify which DC subsets express vaccinal mRNA. To this end, we will use a cre recombinase-expressing mRNA vaccine enabling the genetic labelling of mRNA expressing cells in ROSAloxSTOPloxdTOMATO mice. In these mice, cre-expressing cells express the dTOMATO fluorescent reporter protein. dTOMATO fluorescence will be monitored by flow cytometry and confocal microscopy on tissue section. Single cell RNAseq will be performed to identify the transcriptional profile of DCs interacting with vaccines.

2°) To evaluate vaccine-induced T and B cell responses in vaccine draining lymph nodes. This will be achieved by immunological assays (polyfunctional cytokine secretion assay after peptide specific restimulation, ELISPOT for antibodies against HA protein) using control DC deficient genetic models (using genetic models of DC deficiency available in the lab: Xcr1DTA; pDCDTA; Mgl2DTA). MHCI and MHCII-peptide tetramer assays will be implemented to identify vaccine-specific T cells and analyze their phenotype (effector, circulating memory, precursor for tissue resident memory for CD8+ and their polarization Th1, Tfh). To evaluate the role of DCs subsets in vaccine-induced protection against airborne infection with Influenza virus H1N1 using mice enabling the conditional depletion of DCs during only the vaccination phase (using genetic models of Diphteria Toxin-inducible inducible DC depletion Xcr1DTR; pDCDTR, Mgl2DTR).

3°) To explore novel avenues to improve DC-dependent T and B cell responses to mRNA vaccines by modifying lipid composition of LNPs and/or embedding non antigenic mRNA modifying DC function.

Profile
We are looking for highly motivated individuals considering pursuing their M2 with a PhD in vaccine immunology.
The candidate is expected to have:

  • A keen interest for adaptive immunity, anti-infectious vaccines and vaccine technology.
  • Motivation to work with pre-clinical model of vaccination and infection based on animal experimentation.
  • English speaking and ability to work in a cooperative, multi-cultural and multi-disciplinary environment.
  • Dynamism, self-organization, autonomy and drive.

Interest for computing biology (R programming, image analysis) will be an additional asset.

Contact & applications:
Applications should be sent to pierre.guermonprez@pasteur.fr
“Dendritic cells and adaptive immunity” Unit, Immunology Department, Institut Pasteur.
For applications, please provide: 1 CV, the email contact for 2 references.