News - Analyse structurale d’un antigène lié chimiquement à des particules de type virales de formulations vaccinales

Analyse structurale d’un antigène lié chimiquement à des particules de type virales de formulations vaccinales

L’équipe SREP, en collaboration avec les groupes du Dr. G. Pintacuda, Prof. K. Tars, et Prof. K. Jaudzems, a montré que la grande sensibilité et résolution de la RMN du solide à 800 MHz, associée à la technique de Polarisation Dynamique Nucléaire et couplée à l’utilisation du radical Tinypol comme agent de polarisation pour les hauts champs, est un outil performant pour déterminer et comparer la structure d’un antigène sous forme libre et celle de ce même antigène lié chimiquement aux agents de formulation d’un vaccin. La méthodologie développée ouvre des possibilités nouvelles pour le développement de vaccins mais aussi pour toutes biotechnologies utilisant des biomolécules bioconjuguées.

Structural Analysis of an Antigen Chemically Coupled on Virus-Like Particles in Vaccine Formulation

Kristaps Jaudzems, Anna Kirsteina, Tobias Schubeis, Gilles Casano, Olivier Ouari, Janis Bogans, Andris Kazaks, Kaspars Tars, Anne Lesage, Guido Pintacuda,
Angewandte Chemie-International Edition, 60 12847-12851 (2021)

Structure determination of adjuvant-coupled antigens is essential for rational vaccine development but has so far been hampered by the relatively low antigen content in vaccine formulations and by their heterogeneous composition. Here we show that magic-angle spinning (MAS) solid-state NMR can be used to assess the structure of the influenza virus hemagglutinin stalk long alpha helix antigen, both in its free, unformulated form and once chemically coupled to the surface of large virus-like particles (VLPs). The sensitivity boost provided by high-field dynamic nuclear polarization (DNP) and proton detection at fast MAS rates allows to overcome the penalty associated with the antigen dilution. Comparison of the MAS NMR fingerprints between the free and VLP-coupled forms of the antigen provides structural evidence of the conservation of its native fold upon bioconjugation. This work demonstrates that high-sensitivity MAS NMR is ripe to play a major role in vaccine design, formulation studies, and manufacturing process development.

Structure determination of adjuvant‐coupled antigens is essential for rational vaccine development but has so far been hampered by the relatively low antigen content in vaccine formulations and by their heterogeneous composition. Here we show that magic‐angle spinning (MAS) solid‐state NMR can be used to assess the structure of the influenza virus hemagglutinin stalk long alpha helix antigen, both in its free, unformulated form and once chemically coupled to the surface of large virus‐like particles (VLPs). The sensitivity boost provided by high‐field dynamic nuclear polarization (DNP) and proton‐detection at fast MAS rates allows to overcome the penalty associated to the antigen dilution. Comparison of the MAS NMR fingerprints between the free and VLP‐coupled forms of the antigen provides structural evidence of the conservation of its native fold upon bio‐conjugation. This work demonstrates that high‐sensitivity MAS NMR is ripe to play a major role in vaccine design, formulation studies and manufacturing process development.

Reference :

Kristaps Jaudzems, Anna Kirsteina, Tobias Schubeis, Gilles Casano, Olivier Ouari, Janis Bogans, Andris Kazaks, Kaspars Tars, Anne Lesage, Guido Pintacuda Structural Analysis of an Antigen Chemically‐Coupled on Virus‐Like Particles in Vaccine Formulation, Angew. Chem. Int. Ed. 2021, 10.1002/anie.202013189.