Lainscek, Dusko and Fink, Tina and Forstneric, Vida and Hafner-Bratkovic, Iva and Orehek, Sara and Strmsek, Ziga and Mancek-Keber, Mateja and Pecan, Peter and Esih, Hana and Malensek, Spela and Aupic, Jana and Dekleva, Petra and Plaper, Tjasa and Vidmar, Sara and Kadunc, Lucija and Bencina, Mojca and Omersa, Neza and Anderluh, Gregor and Pojer, Florence and Lau, Kelvin and Hacker, David and Correia, Bruno E. and Peterhoff, David and Wagner, Ralf and Bergant, Valter and Herrmann, Alexander and Pichlmair, Andreas and Jerala, Roman (2021) A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response. VACCINES, 9 (5): 431. ISSN , 2076-393X
Full text not available from this repository. (Request a copy)Abstract
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 beta-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 beta-annulus peptide scaffold, which itself triggered a minimal response in contrast to larger scaffolds. The beta-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 beta-annulus peptide for vaccine design.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LUMAZINE SYNTHASE; DNA VACCINE; PROTEIN; DESIGN; DELIVERY; NANOPARTICLES; ACTIVATION; MECHANISMS; DOMAIN; SARS-CoV-2; RBD-bann; nano-scaffolding domains; vaccine; T-cell response |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Sep 2022 12:48 |
| Last Modified: | 13 Sep 2022 12:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47324 |
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