tetano
Editor, Senior Moderator
Cell Rep
. 2023 Mar 6;42(3):112266.
doi: 10.1016/j.celrep.2023.112266. Online ahead of print.
Design of a stabilized RBD enables potently neutralizing SARS-CoV-2 single-component nanoparticle vaccines
Thayne H Dickey[SUP] 1 [/SUP], Rui Ma[SUP] 1 [/SUP], Sachy Orr-Gonzalez[SUP] 1 [/SUP], Tarik Ouahes[SUP] 1 [/SUP], Palak Patel[SUP] 1 [/SUP], Holly McAleese[SUP] 1 [/SUP], Brandi Butler[SUP] 1 [/SUP], Elizabeth Eudy[SUP] 2 [/SUP], Brett Eaton[SUP] 2 [/SUP], Michael Murphy[SUP] 2 [/SUP], Jennifer L Kwan[SUP] 3 [/SUP], Nichole D Salinas[SUP] 1 [/SUP], Michael R Holbrook[SUP] 2 [/SUP], Lynn E Lambert[SUP] 1 [/SUP], Niraj H Tolia[SUP] 4 [/SUP]
Affiliations
Abstract
Waning immunity and emerging variants necessitate continued vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Improvements in vaccine safety, tolerability, and ease of manufacturing would benefit these efforts. Here, we develop a potent and easily manufactured nanoparticle vaccine displaying the spike receptor-binding domain (RBD). Computational design to stabilize the RBD, eliminate glycosylation, and focus the immune response to neutralizing epitopes results in an RBD immunogen that resolves issues hindering the efficient nanoparticle display of the native RBD. This non-glycosylated RBD can be genetically fused to diverse single-component nanoparticle platforms, maximizing manufacturing ease and flexibility. All engineered RBD nanoparticles elicit potently neutralizing antibodies in mice that far exceed monomeric RBDs. A 60-copy particle (noNAG-RBD-E2p) also elicits potently neutralizing antibodies in non-human primates. The neutralizing antibody titers elicited by noNAG-RBD-E2p are comparable to a benchmark stabilized spike antigen and reach levels against Omicron BA.5 that suggest that it would provide protection against emerging variants.
Keywords: CP: Immunology; CP: Microbiology; SPEEDesign; glycosylation; immunogen; nanoparticle; stabilized; structural vaccinology; structure-based design.
. 2023 Mar 6;42(3):112266.
doi: 10.1016/j.celrep.2023.112266. Online ahead of print.
Design of a stabilized RBD enables potently neutralizing SARS-CoV-2 single-component nanoparticle vaccines
Thayne H Dickey[SUP] 1 [/SUP], Rui Ma[SUP] 1 [/SUP], Sachy Orr-Gonzalez[SUP] 1 [/SUP], Tarik Ouahes[SUP] 1 [/SUP], Palak Patel[SUP] 1 [/SUP], Holly McAleese[SUP] 1 [/SUP], Brandi Butler[SUP] 1 [/SUP], Elizabeth Eudy[SUP] 2 [/SUP], Brett Eaton[SUP] 2 [/SUP], Michael Murphy[SUP] 2 [/SUP], Jennifer L Kwan[SUP] 3 [/SUP], Nichole D Salinas[SUP] 1 [/SUP], Michael R Holbrook[SUP] 2 [/SUP], Lynn E Lambert[SUP] 1 [/SUP], Niraj H Tolia[SUP] 4 [/SUP]
Affiliations
- PMID: 36943870
- DOI: 10.1016/j.celrep.2023.112266
Abstract
Waning immunity and emerging variants necessitate continued vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Improvements in vaccine safety, tolerability, and ease of manufacturing would benefit these efforts. Here, we develop a potent and easily manufactured nanoparticle vaccine displaying the spike receptor-binding domain (RBD). Computational design to stabilize the RBD, eliminate glycosylation, and focus the immune response to neutralizing epitopes results in an RBD immunogen that resolves issues hindering the efficient nanoparticle display of the native RBD. This non-glycosylated RBD can be genetically fused to diverse single-component nanoparticle platforms, maximizing manufacturing ease and flexibility. All engineered RBD nanoparticles elicit potently neutralizing antibodies in mice that far exceed monomeric RBDs. A 60-copy particle (noNAG-RBD-E2p) also elicits potently neutralizing antibodies in non-human primates. The neutralizing antibody titers elicited by noNAG-RBD-E2p are comparable to a benchmark stabilized spike antigen and reach levels against Omicron BA.5 that suggest that it would provide protection against emerging variants.
Keywords: CP: Immunology; CP: Microbiology; SPEEDesign; glycosylation; immunogen; nanoparticle; stabilized; structural vaccinology; structure-based design.