tetano
Editor, Senior Moderator
Cell Rep
. 2023 Oct 12:113248.
doi: 10.1016/j.celrep.2023.113248. Online ahead of print. Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice
David R Martinez[SUP] 1 [/SUP], Alexandra Schäfer[SUP] 2 [/SUP], Tyler D Gavitt[SUP] 3 [/SUP], Michael L Mallory[SUP] 2 [/SUP], Esther Lee[SUP] 3 [/SUP], Nicholas J Catanzaro[SUP] 2 [/SUP], Haiyan Chen[SUP] 3 [/SUP], Kendra Gully[SUP] 2 [/SUP], Trevor Scobey[SUP] 2 [/SUP], Pooja Korategere[SUP] 3 [/SUP], Alecia Brown[SUP] 3 [/SUP], Lena Smith[SUP] 3 [/SUP], Robert Parks[SUP] 3 [/SUP], Maggie Barr[SUP] 3 [/SUP], Amanda Newman[SUP] 3 [/SUP], Cindy Bowman[SUP] 3 [/SUP], John M Powers[SUP] 2 [/SUP], Erik J Soderblom[SUP] 4 [/SUP], Katayoun Mansouri[SUP] 3 [/SUP], Robert J Edwards[SUP] 3 [/SUP], Ralph S Baric[SUP] 5 [/SUP], Barton F Haynes[SUP] 6 [/SUP], Kevin O Saunders[SUP] 7 [/SUP]
Affiliations
The emergence of three highly pathogenic human coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern respiratory syndrome (MERS)-CoV in 2012, and SARS-CoV-2 in 2019-underlines the need to develop broadly active vaccines against the Merbecovirus and Sarbecovirus betacoronavirus subgenera. While SARS-CoV-2 vaccines protect against severe COVID-19, they do not protect against other sarbecoviruses or merbecoviruses. Here, we vaccinate mice with a trivalent sortase-conjugate nanoparticle (scNP) vaccine containing the SARS-CoV-2, RsSHC014, and MERS-CoV receptor-binding domains (RBDs), which elicited live-virus neutralizing antibody responses. The trivalent RBD scNP elicited serum neutralizing antibodies against bat zoonotic Wuhan Institute of Virology-1 (WIV-1)-CoV, SARS-CoV, SARS-CoV-2 BA.1, SARS-CoV-2 XBB.1.5, and MERS-CoV live viruses. The monovalent SARS-CoV-2 RBD scNP vaccine only protected against Sarbecovirus challenge, whereas the trivalent RBD scNP vaccine protected against both Merbecovirus and Sarbecovirus challenge in highly pathogenic and lethal mouse models. This study demonstrates proof of concept for a single pan-sarbecovirus/pan-merbecovirus vaccine that protects against three highly pathogenic human coronaviruses spanning two betacoronavirus subgenera.
Keywords: CP: Immunology; MERS-CoV; SARS-CoV; SARS-CoV-2; bat coronavirus; nanoparticle; neutralization; receptor-binding domain; universal vaccine.
. 2023 Oct 12:113248.
doi: 10.1016/j.celrep.2023.113248. Online ahead of print. Vaccine-mediated protection against Merbecovirus and Sarbecovirus challenge in mice
David R Martinez[SUP] 1 [/SUP], Alexandra Schäfer[SUP] 2 [/SUP], Tyler D Gavitt[SUP] 3 [/SUP], Michael L Mallory[SUP] 2 [/SUP], Esther Lee[SUP] 3 [/SUP], Nicholas J Catanzaro[SUP] 2 [/SUP], Haiyan Chen[SUP] 3 [/SUP], Kendra Gully[SUP] 2 [/SUP], Trevor Scobey[SUP] 2 [/SUP], Pooja Korategere[SUP] 3 [/SUP], Alecia Brown[SUP] 3 [/SUP], Lena Smith[SUP] 3 [/SUP], Robert Parks[SUP] 3 [/SUP], Maggie Barr[SUP] 3 [/SUP], Amanda Newman[SUP] 3 [/SUP], Cindy Bowman[SUP] 3 [/SUP], John M Powers[SUP] 2 [/SUP], Erik J Soderblom[SUP] 4 [/SUP], Katayoun Mansouri[SUP] 3 [/SUP], Robert J Edwards[SUP] 3 [/SUP], Ralph S Baric[SUP] 5 [/SUP], Barton F Haynes[SUP] 6 [/SUP], Kevin O Saunders[SUP] 7 [/SUP]
Affiliations
- PMID: 37858337
- DOI: 10.1016/j.celrep.2023.113248
The emergence of three highly pathogenic human coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern respiratory syndrome (MERS)-CoV in 2012, and SARS-CoV-2 in 2019-underlines the need to develop broadly active vaccines against the Merbecovirus and Sarbecovirus betacoronavirus subgenera. While SARS-CoV-2 vaccines protect against severe COVID-19, they do not protect against other sarbecoviruses or merbecoviruses. Here, we vaccinate mice with a trivalent sortase-conjugate nanoparticle (scNP) vaccine containing the SARS-CoV-2, RsSHC014, and MERS-CoV receptor-binding domains (RBDs), which elicited live-virus neutralizing antibody responses. The trivalent RBD scNP elicited serum neutralizing antibodies against bat zoonotic Wuhan Institute of Virology-1 (WIV-1)-CoV, SARS-CoV, SARS-CoV-2 BA.1, SARS-CoV-2 XBB.1.5, and MERS-CoV live viruses. The monovalent SARS-CoV-2 RBD scNP vaccine only protected against Sarbecovirus challenge, whereas the trivalent RBD scNP vaccine protected against both Merbecovirus and Sarbecovirus challenge in highly pathogenic and lethal mouse models. This study demonstrates proof of concept for a single pan-sarbecovirus/pan-merbecovirus vaccine that protects against three highly pathogenic human coronaviruses spanning two betacoronavirus subgenera.
Keywords: CP: Immunology; MERS-CoV; SARS-CoV; SARS-CoV-2; bat coronavirus; nanoparticle; neutralization; receptor-binding domain; universal vaccine.