tetano
Editor, Senior Moderator
Sci Rep
. 2024 Mar 8;14(1):5735.
doi: 10.1038/s41598-024-56293-x. Impact of SARS-CoV-2 spike stability and RBD exposure on antigenicity and immunogenicity
Lucy Rutten[SUP] 1 [/SUP], Maarten Swart[SUP] 1 [/SUP], Annemart Koornneef[SUP] 1 [/SUP], Pascale Bouchier[SUP] 1 [/SUP], Sven Blokland[SUP] 1 [/SUP], Ava Sadi[SUP] 1 [/SUP], Jarek Juraszek[SUP] 1 [/SUP], Aneesh Vijayan[SUP] 1 [/SUP], Sonja Schmit-Tillemans[SUP] 1 [/SUP], Johan Verspuij[SUP] 1 [/SUP], Ying Choi[SUP] 1 [/SUP], Chenandly E Daal[SUP] 1 [/SUP], Aditya Perkasa[SUP] 1 [/SUP], Shessy Torres Morales[SUP] 2 [/SUP], Sebenzile K Myeni[SUP] 2 [/SUP], Marjolein Kikkert[SUP] 2 [/SUP], Jeroen Tolboom[SUP] 1 [/SUP], Daniëlle van Manen[SUP] 1 [/SUP], Harmjan Kuipers[SUP] 1 [/SUP], Hanneke Schuitemaker[SUP] 1 [/SUP], Roland Zahn[SUP] 1 [/SUP], Johannes P M Langedijk[SUP] 3 4 [/SUP]
Affiliations
The spike protein (S) of SARS-CoV-2 induces neutralizing antibodies and is the key component of current COVID-19 vaccines. The most efficacious COVID-19 vaccines are genetically-encoded spikes with a double proline substitution in the hinge region to stabilize S in the prefusion conformation (S-2P). A subunit vaccine can be a valuable addition to mRNA and viral vector-based vaccines but requires high stability of spike. In addition, further stabilization of the prefusion conformation of spike might improve immunogenicity. To test this, five spike proteins were designed and characterized, ranging from low to high stability. The immunogenicity of these proteins was assessed in mice, demonstrating that a spike (S-closed-2) with a high melting temperature, which still allowed ACE2 binding, induced the highest neutralization titers against homologous and heterologous strains (up to 16-fold higher than the least stabilized spike). In contrast, the most stable spike variant (S-locked), in which the receptor binding domains (RBDs) were locked in a closed conformation and thus not able to breathe, induced relatively low neutralizing antibody titers against heterologous strains. These data demonstrate that S protein stabilization with RBDs exposing highly conserved epitopes may be needed to increase the immunogenicity of spike proteins for future COVID-19 vaccines.
. 2024 Mar 8;14(1):5735.
doi: 10.1038/s41598-024-56293-x. Impact of SARS-CoV-2 spike stability and RBD exposure on antigenicity and immunogenicity
Lucy Rutten[SUP] 1 [/SUP], Maarten Swart[SUP] 1 [/SUP], Annemart Koornneef[SUP] 1 [/SUP], Pascale Bouchier[SUP] 1 [/SUP], Sven Blokland[SUP] 1 [/SUP], Ava Sadi[SUP] 1 [/SUP], Jarek Juraszek[SUP] 1 [/SUP], Aneesh Vijayan[SUP] 1 [/SUP], Sonja Schmit-Tillemans[SUP] 1 [/SUP], Johan Verspuij[SUP] 1 [/SUP], Ying Choi[SUP] 1 [/SUP], Chenandly E Daal[SUP] 1 [/SUP], Aditya Perkasa[SUP] 1 [/SUP], Shessy Torres Morales[SUP] 2 [/SUP], Sebenzile K Myeni[SUP] 2 [/SUP], Marjolein Kikkert[SUP] 2 [/SUP], Jeroen Tolboom[SUP] 1 [/SUP], Daniëlle van Manen[SUP] 1 [/SUP], Harmjan Kuipers[SUP] 1 [/SUP], Hanneke Schuitemaker[SUP] 1 [/SUP], Roland Zahn[SUP] 1 [/SUP], Johannes P M Langedijk[SUP] 3 4 [/SUP]
Affiliations
- PMID: 38459086
- PMCID: PMC10923862
- DOI: 10.1038/s41598-024-56293-x
The spike protein (S) of SARS-CoV-2 induces neutralizing antibodies and is the key component of current COVID-19 vaccines. The most efficacious COVID-19 vaccines are genetically-encoded spikes with a double proline substitution in the hinge region to stabilize S in the prefusion conformation (S-2P). A subunit vaccine can be a valuable addition to mRNA and viral vector-based vaccines but requires high stability of spike. In addition, further stabilization of the prefusion conformation of spike might improve immunogenicity. To test this, five spike proteins were designed and characterized, ranging from low to high stability. The immunogenicity of these proteins was assessed in mice, demonstrating that a spike (S-closed-2) with a high melting temperature, which still allowed ACE2 binding, induced the highest neutralization titers against homologous and heterologous strains (up to 16-fold higher than the least stabilized spike). In contrast, the most stable spike variant (S-locked), in which the receptor binding domains (RBDs) were locked in a closed conformation and thus not able to breathe, induced relatively low neutralizing antibody titers against heterologous strains. These data demonstrate that S protein stabilization with RBDs exposing highly conserved epitopes may be needed to increase the immunogenicity of spike proteins for future COVID-19 vaccines.