In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 9 ( 2023-9-18), p. e1011659-
Abstract:
SARS-CoV-2 variants with severe immune evasion are a major challenge for COVID-19 prevention, especially the circulating Omicron XBB/BQ.1.1/BF.7 strains. Thus, the next-generation of broad-spectrum vaccines are urgently needed. Previously, we developed a COVID-19 protein subunit vaccine, ZF2001, based on the RBD-homodimer as the immunogen. To adapt SARS-CoV-2 variants, we developed chimeric RBD-heterodimers to induce broad immune responses. In this study, we further explored the concept of tandem RBD homotrimer and heterotrimer. Prototype SARS-CoV-2 RBD-homotrimer, prototype-Delta-BA.1 (PDO) RBD-heterotrimer and Delta-BA.2-BA.5 (DBA2BA5) RBD-heterotrimer were designed. Biochemical and cryo-EM structural characterization demonstrated total epitope exposure of the RBD-trimers. In mouse experiments, PDO and DBA2BA5 elicited broad SARS-CoV-2 neutralization. Potent protection against SARS-CoV-2 variants was observed in challenge assays and was correlated with neutralizing antibody titer. This study validated the design strategy of tandem RBD-heterotrimers as multivalent immunogens and presented a promising vaccine candidate, DBA2BA5, eliciting broad-spectrum immune responses, including against the circulating XBB/BF.7/BQ.1.1.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011659
DOI:
10.1371/journal.ppat.1011659.g001
DOI:
10.1371/journal.ppat.1011659.g002
DOI:
10.1371/journal.ppat.1011659.g003
DOI:
10.1371/journal.ppat.1011659.g004
DOI:
10.1371/journal.ppat.1011659.g005
DOI:
10.1371/journal.ppat.1011659.g006
DOI:
10.1371/journal.ppat.1011659.s001
DOI:
10.1371/journal.ppat.1011659.s002
DOI:
10.1371/journal.ppat.1011659.s003
DOI:
10.1371/journal.ppat.1011659.s004
DOI:
10.1371/journal.ppat.1011659.s005
DOI:
10.1371/journal.ppat.1011659.s006
DOI:
10.1371/journal.ppat.1011659.s007
DOI:
10.1371/journal.ppat.1011659.s008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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