{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Miranda MC"],"funding":["NIAID NIH HHS","U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases","U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)","NIGMS NIH HHS"],"pagination":["184"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11461925"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(1)"],"pubmed_abstract":["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<sup>TM</sup>. Here we characterize the biophysical properties, stability, antigenicity, and immunogenicity of RBD-NP immunogens incorporating mutations from the B.1.351 (β) and P.1 (γ) 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 β and γ 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."],"journal":["NPJ vaccines"],"pubmed_title":["Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens."],"pmcid":["PMC11461925"],"funding_grant_id":["DP1 AI158186","HHSN272201700059C","P01AI167966","P01 AI167966","R01 GM120553"],"pubmed_authors":["Sydeman C","Johnson M","Valdez A","Kraft JC","Lee K","Palser A","Ogohara C","Murphy M","King NP","Corti D","Sprouse KR","Stewart C","Miranda MC","Pham M","Carter L","Fiala B","Kepl E","Veesler D","Ravichandran R","Chen C","Pettie D","Walls AC","Kellam P","Ellis D","Wrenn S","Navarro MJ"],"additional_accession":[]},"is_claimable":false,"name":"Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens.","description":"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<sup>TM</sup>. Here we characterize the biophysical properties, stability, antigenicity, and immunogenicity of RBD-NP immunogens incorporating mutations from the B.1.351 (β) and P.1 (γ) 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 β and γ 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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2026-06-23T03:17:58.588Z","creation":"2025-04-06T22:32:26.611Z"},"accession":"S-EPMC11461925","cross_references":{"pubmed":["39379400"],"doi":["10.1038/s41541-024-00982-1"]}}