tetano
Editor, Senior Moderator
Biotechnol J
. 2023 Jun 10;e2300130.
doi: 10.1002/biot.202300130. Online ahead of print. A bioengineered pseudovirus nanoparticle displaying SARS-CoV 2 RBD fully protects mice from mortality and weight loss caused by SARS-CoV 2 challenge
Ming Xia[SUP] 1 [/SUP], Krisangel López[SUP] 2 [/SUP], Frank S Vago[SUP] 3 [/SUP], Pengwei Huang[SUP] 1 [/SUP], Dawn I Auguste[SUP] 2 [/SUP], Wen Jiang[SUP] 3 [/SUP], Albert J Auguste[SUP] 2 4 [/SUP], Ming Tan[SUP] 1 5 [/SUP]
Affiliations
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable morbidity and mortality worldwide. Although authorized COVID-19 vaccines have been shown highly effective, their significantly lower efficacy against heterologous variants, and the rapid decrease of vaccine-elicited immunity raises serious concerns, calling for improved vaccine tactics. To this end, we have generated a pseudovirus nanoparticle (PVNP) displaying the receptor-binding domains (RBDs) of SARS-CoV-2 spike, named S-RBD, and shown it as a promising COVID-19 vaccine candidate. The S-RBD PVNP was produced using both prokaryotic and eukaryotic systems. A three-dimensional structural model of the S-RBD PVNPs was built based on the known structures of the S[SUB]60[/SUB] particle and RBDs, revealing an S[SUB]60[/SUB] particle-based icosahedral symmetry with multiple surface-displayed RBDs that retain authentic conformations and receptor-binding functions. The PVNP is highly immunogenic, eliciting high titers of RBD-specific IgG and neutralizing antibodies in mice. The S-RBD PVNP demonstrated exceptional protective efficacy, and fully (100%) protected K18-hACE2 mice from mortality and weight loss after a lethal SARS-CoV-2 challenge, supporting the S-RBD PVNPs as a potent COVID-19 vaccine candidate. By contrast, a PVNP displaying the N-terminal domain (NTD) of SARS-CoV-2 spike exhibited only 50% protective efficacy. Since the RBD antigens of our PVNP vaccine are adjustable as needed to address the emergence of future variants, and various S-RBD PVNPs can be combined as a cocktail vaccine for broad efficacy, these non-replicating PVNPs offer a flexible platform for a safe, effective COVID-19 vaccine with minimal manufacturing cost and time. This article is protected by copyright. All rights reserved.
Keywords: COVID-19; SARS-CoV-2; pseudovirus nanoparticle; receptor binding domain; vaccine; viral receptor.
. 2023 Jun 10;e2300130.
doi: 10.1002/biot.202300130. Online ahead of print. A bioengineered pseudovirus nanoparticle displaying SARS-CoV 2 RBD fully protects mice from mortality and weight loss caused by SARS-CoV 2 challenge
Ming Xia[SUP] 1 [/SUP], Krisangel López[SUP] 2 [/SUP], Frank S Vago[SUP] 3 [/SUP], Pengwei Huang[SUP] 1 [/SUP], Dawn I Auguste[SUP] 2 [/SUP], Wen Jiang[SUP] 3 [/SUP], Albert J Auguste[SUP] 2 4 [/SUP], Ming Tan[SUP] 1 5 [/SUP]
Affiliations
- PMID: 37300425
- DOI: 10.1002/biot.202300130
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable morbidity and mortality worldwide. Although authorized COVID-19 vaccines have been shown highly effective, their significantly lower efficacy against heterologous variants, and the rapid decrease of vaccine-elicited immunity raises serious concerns, calling for improved vaccine tactics. To this end, we have generated a pseudovirus nanoparticle (PVNP) displaying the receptor-binding domains (RBDs) of SARS-CoV-2 spike, named S-RBD, and shown it as a promising COVID-19 vaccine candidate. The S-RBD PVNP was produced using both prokaryotic and eukaryotic systems. A three-dimensional structural model of the S-RBD PVNPs was built based on the known structures of the S[SUB]60[/SUB] particle and RBDs, revealing an S[SUB]60[/SUB] particle-based icosahedral symmetry with multiple surface-displayed RBDs that retain authentic conformations and receptor-binding functions. The PVNP is highly immunogenic, eliciting high titers of RBD-specific IgG and neutralizing antibodies in mice. The S-RBD PVNP demonstrated exceptional protective efficacy, and fully (100%) protected K18-hACE2 mice from mortality and weight loss after a lethal SARS-CoV-2 challenge, supporting the S-RBD PVNPs as a potent COVID-19 vaccine candidate. By contrast, a PVNP displaying the N-terminal domain (NTD) of SARS-CoV-2 spike exhibited only 50% protective efficacy. Since the RBD antigens of our PVNP vaccine are adjustable as needed to address the emergence of future variants, and various S-RBD PVNPs can be combined as a cocktail vaccine for broad efficacy, these non-replicating PVNPs offer a flexible platform for a safe, effective COVID-19 vaccine with minimal manufacturing cost and time. This article is protected by copyright. All rights reserved.
Keywords: COVID-19; SARS-CoV-2; pseudovirus nanoparticle; receptor binding domain; vaccine; viral receptor.