期刊
VACCINES
卷 9, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/vaccines9050431
关键词
SARS-CoV-2; RBD-bann; nano-scaffolding domains; vaccine; T-cell response
资金
- Slovenian Research Agency [P4-0176, Z3-9276, Z3-9260]
- H2020 project Virofight
- ERC AdG project MaCChines
- German Research Foundation [TRR179/TP11, TRR237/A07]
- German Federal Ministry of Education and Research (COVINET)
- ERC-CoG project ProDAP
This study compared the efficiency of different nanoscaffolding platforms for SARS-CoV-2 vaccine design, finding that fusion of RBD with the small beta-annulus peptide scaffold significantly enhanced antibody titers and virus neutralization, providing a new approach for vaccine design.
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.
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