tetano
Editor, Senior Moderator
NPJ Vaccines
. 2024 Oct 8;9(1):184.
doi: 10.1038/s41541-024-00982-1. Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens
Marcos C Miranda[SUP] #[/SUP][SUP] 1 2 [/SUP], Elizabeth Kepl[SUP] #[/SUP][SUP] 1 2 [/SUP], Mary Jane Navarro[SUP] 1 [/SUP], Chengbo Chen[SUP] 3 4 [/SUP], Max Johnson[SUP] 1 2 [/SUP], Kaitlin R Sprouse[SUP] 1 [/SUP], Cameron Stewart[SUP] 1 [/SUP], Anne Palser[SUP] 5 [/SUP], Adian Valdez[SUP] 1 2 [/SUP], Deleah Pettie[SUP] 1 2 [/SUP], Claire Sydeman[SUP] 1 2 [/SUP], Cassandra Ogohara[SUP] 1 2 [/SUP], John C Kraft[SUP] 1 2 [/SUP], Minh Pham[SUP] 1 2 [/SUP], Michael Murphy[SUP] 1 2 [/SUP], Sam Wrenn[SUP] 1 2 [/SUP], Brooke Fiala[SUP] 1 2 [/SUP], Rashmi Ravichandran[SUP] 1 2 [/SUP], Daniel Ellis[SUP] 1 2 [/SUP], Lauren Carter[SUP] 1 2 [/SUP], Davide Corti[SUP] 6 [/SUP], Paul Kellam[SUP] 5 7 [/SUP], Kelly Lee[SUP] 3 4 [/SUP], Alexandra C Walls[SUP] 1 [/SUP], David Veesler[SUP] 8 9 [/SUP], Neil P King[SUP] 10 11 [/SUP]
Affiliations
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.
. 2024 Oct 8;9(1):184.
doi: 10.1038/s41541-024-00982-1. Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens
Marcos C Miranda[SUP] #[/SUP][SUP] 1 2 [/SUP], Elizabeth Kepl[SUP] #[/SUP][SUP] 1 2 [/SUP], Mary Jane Navarro[SUP] 1 [/SUP], Chengbo Chen[SUP] 3 4 [/SUP], Max Johnson[SUP] 1 2 [/SUP], Kaitlin R Sprouse[SUP] 1 [/SUP], Cameron Stewart[SUP] 1 [/SUP], Anne Palser[SUP] 5 [/SUP], Adian Valdez[SUP] 1 2 [/SUP], Deleah Pettie[SUP] 1 2 [/SUP], Claire Sydeman[SUP] 1 2 [/SUP], Cassandra Ogohara[SUP] 1 2 [/SUP], John C Kraft[SUP] 1 2 [/SUP], Minh Pham[SUP] 1 2 [/SUP], Michael Murphy[SUP] 1 2 [/SUP], Sam Wrenn[SUP] 1 2 [/SUP], Brooke Fiala[SUP] 1 2 [/SUP], Rashmi Ravichandran[SUP] 1 2 [/SUP], Daniel Ellis[SUP] 1 2 [/SUP], Lauren Carter[SUP] 1 2 [/SUP], Davide Corti[SUP] 6 [/SUP], Paul Kellam[SUP] 5 7 [/SUP], Kelly Lee[SUP] 3 4 [/SUP], Alexandra C Walls[SUP] 1 [/SUP], David Veesler[SUP] 8 9 [/SUP], Neil P King[SUP] 10 11 [/SUP]
Affiliations
- PMID: 39379400
- PMCID: PMC11461925
- DOI: 10.1038/s41541-024-00982-1
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.