A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response
| Autor: | Mateja Manček-Keber, Florence Pojer, Alexander Herrmann, Tina Fink, Vida Forstnerič, Gregor Anderluh, Duško Lainšček, Roman Jerala, David L. Hacker, Hana Esih, Peter Pečan, Lucija Kadunc, Tjaša Plaper, Žiga Strmšek, Neža Omersa, Špela Malenšek, Andreas Pichlmair, Petra Dekleva, Mojca Benčina, Bruno E. Correia, David Peterhoff, Kelvin Lau, Jana Aupič, Sara Vidmar, Valter Bergant, Sara Orehek, Iva Hafner-Bratkovič, Ralf Wagner |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
animal diseases viruses Immunology chemical and pharmacologic phenomena Neutralization Article law.invention 03 medical and health sciences 0302 clinical medicine Immune system Antigen nano-scaffolding domains Immunity law vaccine Drug Discovery Pharmacology (medical) Pharmacology biology Chemistry SARS-CoV-2 biochemical phenomena metabolism and nutrition Acquired immune system Virology 3. Good health 030104 developmental biology Infectious Diseases Immunization T-cell response biology.protein Recombinant DNA bacteria Medicine Antibody 030217 neurology & neurosurgery RBD-bann |
| Zdroj: | Vaccines, Vol 9, Iss 431, p 431 (2021) Vaccines Volume 9 Issue 5 |
| Popis: | The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens however, antibodies are also generated against the scaffold, which may impair subsequent vaccination. In order to compare polypeptide scaffolds of different size and oligomerization state with respect to their efficiency, including anti-scaffold immunity, we compared several strategies of presentation of the RBD domain of the SARS-CoV-2 spike protein, an antigen aiming to generate neutralizing antibodies. A comparison of several genetic fusions of RBD to different nanoscaffolding domains (foldon, ferritin, lumazine synthase, and β-annulus peptide) delivered as DNA plasmids demonstrated a strongly augmented immune response, with high titers of neutralizing antibodies and a robust T-cell response in mice. Antibody titers and virus neutralization were most potently enhanced by fusion to the small β-annulus peptide scaffold, which itself triggered a minimal response in contrast to larger scaffolds. The β-annulus fused RBD protein increased residence in lymph nodes and triggered the most potent viral neutralization in immunization by a recombinant protein. Results of the study support the use of a nanoscaffolding platform using the β-annulus peptide for vaccine design. |
| Databáze: | OpenAIRE |
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