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Basic Characteristics of Mutations
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Mutation Site
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Y365F |
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Mutation Site Sentence
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We generated RBD-NPs displaying RBDs from the Wu-1, B.1.351 (β), and P.1 (γ) (K417N/T, E484K, N501Y) lineages with and without the previously reported “Rpk9” stabilizing mutations to the linoleic binding pocket (Y365F, F392W, V395I)20, as these were the dominant circulating strains with prominent escape mutations prior to the Omicron lineages (Fig. 1B). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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39379400
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Title
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Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens
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Author
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Miranda MC,Kepl E,Navarro MJ,Chen C,Johnson M,Sprouse KR,Stewart C,Palser A,Valdez A,Pettie D,Sydeman C,Ogohara C,Kraft JC,Pham M,Murphy M,Wrenn S,Fiala B,Ravichandran R,Ellis D,Carter L,Corti D,Kellam P,Lee K,Walls AC,Veesler D,King NP
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Journal
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NPJ vaccines
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Journal Info
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2024 Oct 8;9(1):184
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Abstract
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We previously described a two-component protein nanoparticle vaccine platform that displays 60 copies of the SARS-CoV-2 spike protein RBD (RBD-NP). The vaccine, when adjuvanted with AS03, was shown to elicit robust neutralizing antibody and CD4 T cell responses in Phase I/II clinical trials, met its primary co-endpoints in a Phase III trial, and has been licensed by multiple regulatory authorities under the brand name SKYCovione(TM). Here we characterize the biophysical properties, stability, antigenicity, and immunogenicity of RBD-NP immunogens incorporating mutations from the B.1.351 (beta) and P.1 (gamma) variants of concern (VOCs) that emerged in 2020. We also show that the RBD-NP platform can be adapted to the Omicron strains BA.5 and XBB.1.5. We compare beta and gamma variant and E484K point mutant nanoparticle immunogens to the nanoparticle displaying the Wu-1 RBD, as well as to soluble prefusion-stabilized (HexaPro) spike trimers harboring VOC-derived mutations. We find the properties of immunogens based on different SARS-CoV-2 variants can differ substantially, which could affect the viability of variant vaccine development. Introducing stabilizing mutations in the linoleic acid binding site of the RBD-NPs resulted in increased physical stability compared to versions lacking the stabilizing mutations without deleteriously affecting immunogenicity. The RBD-NP immunogens and HexaPro trimers, as well as combinations of VOC-based immunogens, elicited comparable levels of neutralizing antibodies against distinct VOCs. Our results demonstrate that RBD-NP-based vaccines can elicit neutralizing antibody responses against SARS-CoV-2 variants and can be rapidly designed and stabilized, demonstrating the potential of two-component RBD-NPs as a platform for the development of broadly protective coronavirus vaccines.
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Sequence Data
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-
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