tetano
Editor, Senior Moderator
Cell Rep
. 2024 Dec 6;43(12):115036.
doi: 10.1016/j.celrep.2024.115036. Online ahead of print. Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV
Cara W Chao[SUP] 1 [/SUP], Kaitlin R Sprouse[SUP] 2 [/SUP], Marcos C Miranda[SUP] 3 [/SUP], Nicholas J Catanzaro[SUP] 4 [/SUP], Miranda L Hubbard[SUP] 4 [/SUP], Amin Addetia[SUP] 2 [/SUP], Cameron Stewart[SUP] 2 [/SUP], Jack T Brown[SUP] 2 [/SUP], Annie Dosey[SUP] 3 [/SUP], Adian Valdez[SUP] 3 [/SUP], Rashmi Ravichandran[SUP] 3 [/SUP], Grace G Hendricks[SUP] 3 [/SUP], Maggie Ahlrichs[SUP] 3 [/SUP], Craig Dobbins[SUP] 3 [/SUP], Alexis Hand[SUP] 3 [/SUP], Jackson McGowan[SUP] 3 [/SUP], Boston Simmons[SUP] 3 [/SUP], Catherine Treichel[SUP] 3 [/SUP], Isabelle Willoughby[SUP] 3 [/SUP], Alexandra C Walls[SUP] 2 [/SUP], Andrew T McGuire[SUP] 5 [/SUP], Elizabeth M Leaf[SUP] 3 [/SUP], Ralph S Baric[SUP] 4 [/SUP], Alexandra Schäfer[SUP] 4 [/SUP], David Veesler[SUP] 6 [/SUP], Neil P King[SUP] 7 [/SUP]
Affiliations
Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus that causes severe respiratory illness in humans. There are no licensed vaccines against MERS-CoV and only a few candidates in phase I clinical trials. Here, we develop MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two-component nanoparticles displaying spike (S)-derived antigens induce neutralizing responses and protect mice against challenge with mouse-adapted MERS-CoV. Epitope mapping reveals the dominant responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle elicits antibodies targeting multiple non-overlapping epitopes in the RBD. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.
Keywords: CP: Immunology; EMPEM; MERS-CoV; NTD; RBD; nanoparticle; spike; vaccine.
. 2024 Dec 6;43(12):115036.
doi: 10.1016/j.celrep.2024.115036. Online ahead of print. Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV
Cara W Chao[SUP] 1 [/SUP], Kaitlin R Sprouse[SUP] 2 [/SUP], Marcos C Miranda[SUP] 3 [/SUP], Nicholas J Catanzaro[SUP] 4 [/SUP], Miranda L Hubbard[SUP] 4 [/SUP], Amin Addetia[SUP] 2 [/SUP], Cameron Stewart[SUP] 2 [/SUP], Jack T Brown[SUP] 2 [/SUP], Annie Dosey[SUP] 3 [/SUP], Adian Valdez[SUP] 3 [/SUP], Rashmi Ravichandran[SUP] 3 [/SUP], Grace G Hendricks[SUP] 3 [/SUP], Maggie Ahlrichs[SUP] 3 [/SUP], Craig Dobbins[SUP] 3 [/SUP], Alexis Hand[SUP] 3 [/SUP], Jackson McGowan[SUP] 3 [/SUP], Boston Simmons[SUP] 3 [/SUP], Catherine Treichel[SUP] 3 [/SUP], Isabelle Willoughby[SUP] 3 [/SUP], Alexandra C Walls[SUP] 2 [/SUP], Andrew T McGuire[SUP] 5 [/SUP], Elizabeth M Leaf[SUP] 3 [/SUP], Ralph S Baric[SUP] 4 [/SUP], Alexandra Schäfer[SUP] 4 [/SUP], David Veesler[SUP] 6 [/SUP], Neil P King[SUP] 7 [/SUP]
Affiliations
- PMID: 39644492
- DOI: 10.1016/j.celrep.2024.115036
Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus that causes severe respiratory illness in humans. There are no licensed vaccines against MERS-CoV and only a few candidates in phase I clinical trials. Here, we develop MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two-component nanoparticles displaying spike (S)-derived antigens induce neutralizing responses and protect mice against challenge with mouse-adapted MERS-CoV. Epitope mapping reveals the dominant responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle elicits antibodies targeting multiple non-overlapping epitopes in the RBD. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.
Keywords: CP: Immunology; EMPEM; MERS-CoV; NTD; RBD; nanoparticle; spike; vaccine.