Structural Analysis of an Antigen Chemically Coupled on Virus-Like Particles in Vaccine Formulation.
antigen structure
dynamic nuclear polarization
solid-state NMR spectroscopy
vaccine development
virus-like particle
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
01 06 2021
01 06 2021
Historique:
received:
29
09
2020
pubmed:
23
3
2021
medline:
2
9
2021
entrez:
22
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33750007
doi: 10.1002/anie.202013189
doi:
Substances chimiques
Antigens, Viral
0
Vaccines, Virus-Like Particle
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12847-12851Informations de copyright
© 2021 Wiley-VCH GmbH.
Références
M. F. Bachmann, G. T. Jennings, Nat. Rev. Immunol. 2010, 10, 787-796.
M. F. Bachmann, U. H. Rohrer, T. M. Kündig, K. Bürki, H. Hengartner, R. M. Zinkernagel, Science 1993, 262, 1448-1451.
A. Kirsteina, I. Akopjana, J. Bogans, I. Lieknina, J. Jansons, D. Skrastina, T. Kazaka, K. Tars, I. Isakova-Sivak, D. Mezhenskaya, T. Kotomina, V. Matyushenko, L. Rudenko, A. Kazaks, Vaccines (Basel) 2020, 8, 197.
A. L. Marcinkiewicz, I. Lieknina, S. Kotelovica, X. Yang, P. Kraiczy, U. Pal, Y.-P. Lin, K. Tars, Front. Immunol. 2018, 9, 181.
M. F. Bachmann, A. Zeltins, G. Kalnins, I. Balke, N. Fischer, A. Rostaher, K. Tars, C. Favrot, J. Allergy Clin. Immunol. 2018, 142, 279-281.
J. Cornuz, S. Zwahlen, W. F. Jungi, J. Osterwalder, K. Klingler, G. van Melle, Y. Bangala, I. Guessous, P. Müller, J. Willers, P. Maurer, M. F. Bachmann, T. Cerny, PLoS One 2008, 3, e2547.
G. T. Jennings, M. F. Bachmann, Biol. Chem. 2008, 389, 521-536.
Z. Chen, D. L. Stokes, W. J. Rice, L. R. Jones, J. Biol. Chem. 2003, 278, 48348-48356.
R. J. Duncan, P. D. Weston, R. Wrigglesworth, Anal. Biochem. 1983, 132, 68-73.
J.-P. Demers, P. Fricke, C. Shi, V. Chevelkov, A. Lange, Prog. Nucl. Magn. Reson. Spectrosc. 2018, 109, 51-78.
C. M. Quinn, M. Wang, T. Polenova, Methods Mol. Biol. 2018, 1688, 1-35.
L. Cerofolini, S. Giuntini, E. Ravera, C. Luchinat, F. Berti, M. Fragai, npj Vaccines 2019, 4, 20.
K. Jaudzems, T. Polenova, G. Pintacuda, H. Oschkinat, A. Lesage, J. Struct. Biol. 2019, 206, 90-98.
L. B. Andreas, T. Le Marchand, K. Jaudzems, G. Pintacuda, J. Magn. Reson. 2015, 253, 36-49.
A. Böckmann, M. Ernst, B. H. Meier, J. Magn. Reson. 2015, 253, 71-79.
L. B. Andreas, K. Jaudzems, J. Stanek, D. Lalli, A. Bertarello, T. Le Marchand, D. Cala-De Paepe, S. Kotelovica, I. Akopjana, B. Knott, S. Wegner, F. Engelke, A. Lesage, L. Emsley, K. Tars, T. Herrmann, G. Pintacuda, Proc. Natl. Acad. Sci. USA 2016, 113, 9187-9192.
E. J. Koers, M. P. López-Deber, M. Weingarth, D. Nand, D. T. Hickman, D. Mlaki Ndao, P. Reis, A. Granet, A. Pfeifer, A. Muhs, M. Baldus, Angew. Chem. Int. Ed. 2013, 52, 10905-10908;
Angew. Chem. 2013, 125, 11106-11109.
J. Viger-Gravel, F. M. Paruzzo, C. Cazaux, R. Jabbour, A. Leleu, F. Canini, P. Florian, F. Ronzon, D. Gajan, A. Lesage, Chem. Eur. J. 2020, 26, 8976-8982.
Y. H. Jang, B. L. Seong, Front. Cell. Infect. Microbiol. 2019, 9, 344.
I.-N. Lu, A. Kirsteina, S. Farinelle, S. Willieme, K. Tars, C. P. Muller, A. Kazaks, PLoS One 2018, 13, e0204776.
A. C. Tissot, P. Maurer, J. Nussberger, R. Sabat, T. Pfister, S. Ignatenko, H.-D. Volk, H. Stocker, P. Müller, G. T. Jennings, F. Wagner, M. F. Bachmann, Lancet 2008, 371, 821-827.
K.-M. Beeh, F. Kanniess, F. Wagner, C. Schilder, I. Naudts, A. Hammann-Haenni, J. Willers, H. Stocker, P. Mueller, M. F. Bachmann, W. A. Renner, J. Allergy Clin. Immunol. 2013, 131, 866-874.
I. Bertini, C. Luchinat, G. Parigi, E. Ravera, B. Reif, P. Turano, Proc. Natl. Acad. Sci. USA 2011, 108, 10396-10399.
C. Gardiennet, A. K. Schütz, A. Hunkeler, B. Kunert, L. Terradot, A. Böckmann, B. H. Meier, Angew. Chem. Int. Ed. 2012, 51, 7855-7858;
Angew. Chem. 2012, 124, 7977-7980.
A. E. Bennett, R. G. Griffin, J. H. Ok, S. Vega, J. Chem. Phys. 1992, 96, 8624-8627.
K. Takegoshi, S. Nakamura, T. Terao, Chem. Phys. Lett. 2001, 344, 631-637.
J. Stanek, L. B. Andreas, K. Jaudzems, D. Cala, D. Lalli, A. Bertarello, T. Schubeis, I. Akopjana, S. Kotelovica, K. Tars, A. Pica, S. Leone, D. Picone, Z.-Q. Xu, N. E. Dixon, D. Martinez, M. Berbon, N. El Mammeri, A. Noubhani, S. Saupe, B. Habenstein, A. Loquet, G. Pintacuda, Angew. Chem. Int. Ed. 2016, 55, 15504-15509;
Angew. Chem. 2016, 128, 15730-15735.
P. Güntert, C. Mumenthaler, K. Wüthrich, J. Mol. Biol. 1997, 273, 283-298.
Y. Shen, F. Delaglio, G. Cornilescu, A. Bax, J. Biomol. NMR 2009, 44, 213-223.
A. Lund, G. Casano, G. Menzildjian, M. Kaushik, G. Stevanato, M. Yulikov, R. Jabbour, D. Wisser, M. Renom-Carrasco, C. Thieuleux, F. Bernada, H. Karoui, D. Siri, M. Rosay, I. V. Sergeyev, D. Gajan, M. Lelli, L. Emsley, O. Ouari, A. Lesage, Chem. Sci. 2020, 11, 2810-2818.
K. Jaudzems, A. Bertarello, S. R. Chaudhari, A. Pica, D. Cala-De Paepe, E. Barbet-Massin, A. J. Pell, I. Akopjana, S. Kotelovica, D. Gajan, O. Ouari, K. Tars, G. Pintacuda, A. Lesage, Angew. Chem. Int. Ed. 2018, 57, 7458-7462;
Angew. Chem. 2018, 130, 7580-7584.