Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens

Autor: Marcos C. Miranda, Elizabeth Kepl, Mary Jane Navarro, Chengbo Chen, Max Johnson, Kaitlin R. Sprouse, Cameron Stewart, Anne Palser, Adian Valdez, Deleah Pettie, Claire Sydeman, Cassandra Ogohara, John C. Kraft, Minh Pham, Michael Murphy, Sam Wrenn, Brooke Fiala, Rashmi Ravichandran, Daniel Ellis, Lauren Carter, Davide Corti, Paul Kellam, Kelly Lee, Alexandra C. Walls, David Veesler, Neil P. King
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: npj Vaccines, Vol 9, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 2059-0105
39547078
DOI: 10.1038/s41541-024-00982-1
Popis: 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 SKYCovioneTM. 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.
Databáze: Directory of Open Access Journals
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