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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 1 , Kaitlin R Sprouse 2 , Marcos C Miranda 3 , Nicholas J Catanzaro 4 , Miranda L Hubbard 4 , Amin Addetia 2 , Cameron Stewart 2 , Jack T Brown 2 , Annie Dosey 3 , Adian Valdez 3 , Rashmi Ravichandran 3 , Grace G Hendricks 3 , Maggie Ahlrichs 3 , Craig Dobbins 3 , Alexis Hand 3 , Jackson McGowan 3 , Boston Simmons 3 , Catherine Treichel 3 , Isabelle Willoughby 3 , Alexandra C Walls 2 , Andrew T McGuire 5 , Elizabeth M Leaf 3 , Ralph S Baric 4 , Alexandra Schäfer 4 , David Veesler 6 , Neil P King 7
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 1 , Kaitlin R Sprouse 2 , Marcos C Miranda 3 , Nicholas J Catanzaro 4 , Miranda L Hubbard 4 , Amin Addetia 2 , Cameron Stewart 2 , Jack T Brown 2 , Annie Dosey 3 , Adian Valdez 3 , Rashmi Ravichandran 3 , Grace G Hendricks 3 , Maggie Ahlrichs 3 , Craig Dobbins 3 , Alexis Hand 3 , Jackson McGowan 3 , Boston Simmons 3 , Catherine Treichel 3 , Isabelle Willoughby 3 , Alexandra C Walls 2 , Andrew T McGuire 5 , Elizabeth M Leaf 3 , Ralph S Baric 4 , Alexandra Schäfer 4 , David Veesler 6 , Neil P King 7
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.