# Glycoconjugate synthesis based on non-canonical amino acid incorporation for vaccine purpose

Laura Laneque, Marine Goux-Huet, Typhaine Violo, Annie Lambert, Emilie

Camberlein, Cyrille Grandjean

► To cite this version:

Laura Laneque, Marine Goux-Huet, Typhaine Violo, Annie Lambert, Emilie Camberlein, et al.. Glyco-conjugate synthesis based on non-canonical amino acid incorporation for vaccine purpose. ncAAs-2024 "Noncanonical amino acids (ncAAs): Tools for Biological and Biophysical Investigations", Groupe Français des Peptides et des Protéines, Oct 2024, Paris, France. hal-04857600

HAL Id: hal-04857600

https://hal.science/hal-04857600v1

Submitted on 28 Dec 2024

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Distributed under a Creative Commons Attribution 4.0 International License
# Glycoconjugate synthesis based on non-canonical amino acid incorporation for vaccine purpose

Laura Laneque, Marine Goux, Typhaine Violo, Annie Lambert,¹ Emilie Camberlein,¹
Cyrile Grandjean¹

¹Nantes Université, CNRS, Unité en Sciences Biologiques et Biotechnologies (US2B) UMR6286, 2 chemin de la Houssinière, 44000 Nantes, France
cyrille.grandjean@univ-nantes.fr

Glycoconjugate vaccines have proven their efficacy and safety in combating bacterial infections, particularly in young children.¹ They are composed of purified bacterial polysaccharide or synthetic oligosaccharide mimics thereof covalently linked to a protein referred to as a carrier protein which induces a protective immune response through the recruitment of lymphocytes. Route of glycoconjugate administration, vaccine schedule, dose, nature and length of the carbohydrate antigen, the coupling chemistry and the carbohydrate antigen/carrier protein ratio are all parameters that impact the actual immune response.

Incorporation of non-canonical amino acid (NcAA) in the carrier protein offers a unique opportunity to control the sites at which the carbohydrate antigen is linked to the carrier. This strategy leads to easily-characterized, homogeneous glycoconjugates (in comparison with ill-defined, randomly synthesized current glycoconjugate vaccine generation). It also provides unprecedented tools to study structure-immunogenicity relationships.²

<figure><img src="image_2.png" /><figcaption>Figure: Homogenous conjugate obtained by combined NcAA incorporation and click-chemistry</figcaption></figure>

In addition, NcAA strategy can be envisaged to modify the shape of the glycoconjugate or to introduce further modifications such as the grafting of an adjuvant.

Examples illustrating these aspects will be given based on pneumococcal infection as model disease.

**Acknowledgments:** Région Pays de la Loire "BioSynProt" and "GlycoOuest", ANR-21-CE07-0053 for funding

**References:**

[1] Micoli, F.; Costantino, P.; Adamo, R. *FEMS Microbiol. Rev.* **2018**, *42*, 388–423.

[2] Violo, T.; Lambert, A.; Pillot, A.; Fanuel, M.; Mac-Béar, J.; Broussard, C.; Grandjean, C.; Camberlein, E. *Chemistry* **2023**, *29*(15):e202203497