CE18 - Innovation biomédicale

A new approach to intranasal vaccination. – NOSIMMUNE

Submission summary

The primary goal of this research project is to build and evaluate a new vaccinal protein vector optimized for intranasal vaccination against respiratory infections. This new, bi-functional vector is purposed:

(i) To bind and cross the nasal epithelium in the Nasal Associated Lymphoid Tissue (NALT). This will be achieved by including a Fc portion (CH2 and CH3 domains of immunoglobulins) targeting the transcytosis-competent FcRn receptor.

(ii) To bind and deliver antigens in the endocytic pathway of migratory dendritic cells for efficient antigen presentation to CD8+ and CD4+ T cells by MHCI and MHCII. This will be achieved through a VHH nanobody raised against C-type lectin expressed in migratory DCs.

Our project aims at delivering an in vivo pre-clinical proof-of-principle for this new intranasal vaccine approach.
In a first step, we will produce recombinant proteins carrying influenza A virus (IAV) CD4+ and CD8+ T cell epitopes. We will evaluate if those vaccines ensure the induction of local, long-lasting, broadly reactive T cell responses and protection against infectious challenge using multiple viral strains. Using a collection of mutant vectors (targeting epithelial cells, dendritic cells, both or none), we will determine experimentally which targeting moieties actually contribute to the immunogenicity of the vector.

In a second step, we will evaluate if the principle of mono or bi-specific targeting (epithelial cells and dendritic cells) can be also applied to deliver nanoparticle containing mRNA encoding full-length antigens in vivo to ensure local T cell and IgA responses.

Altogether, this project intends to explore a new approach to deliver antigens to the immune system of the nose using tractable, receptor ligands interactions to induce local and persisting immunity against respiratory infections.

Project coordination

Pierre GUERMONPREZ (Département d'Immunologie)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Biologie cellulaire et Cancer, UMR144
IP Département d'Immunologie
PEMR Physiopathologie et épidémiologie des maladies respiratoires
LBTI LABORATOIRE DE BIOLOGIE TISSULAIRE ET D'INGENIERIE THERAPEUTIQUE

Help of the ANR 727,778 euros
Beginning and duration of the scientific project: October 2023 - 36 Months

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