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

Autor: Jaudzems K; Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga, LV-1006, Latvia., Kirsteina A; Latvian Biomedical Research and Study Centre, Ratsupites 1 k1, Riga, LV-1067, Latvia., Schubeis T; Centre de RMN à Très Hauts Champs de Lyon-UMR 5082 (CNRS, ENS Lyon, UCB Lyon 1), Université de Lyon, 69100, Villeurbanne, France., Casano G; Institut de Chimie Radicalaire, AixMarseille Université, 13013, Marseille, France., Ouari O; Institut de Chimie Radicalaire, AixMarseille Université, 13013, Marseille, France., Bogans J; Latvian Biomedical Research and Study Centre, Ratsupites 1 k1, Riga, LV-1067, Latvia., Kazaks A; Latvian Biomedical Research and Study Centre, Ratsupites 1 k1, Riga, LV-1067, Latvia., Tars K; Latvian Biomedical Research and Study Centre, Ratsupites 1 k1, Riga, LV-1067, Latvia., Lesage A; Centre de RMN à Très Hauts Champs de Lyon-UMR 5082 (CNRS, ENS Lyon, UCB Lyon 1), Université de Lyon, 69100, Villeurbanne, France., Pintacuda G; Centre de RMN à Très Hauts Champs de Lyon-UMR 5082 (CNRS, ENS Lyon, UCB Lyon 1), Université de Lyon, 69100, Villeurbanne, France.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Jun 01; Vol. 60 (23), pp. 12847-12851. Date of Electronic Publication: 2021 May 05.
DOI: 10.1002/anie.202013189
Abstrakt: 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.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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