Cell reports · 2024
Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV.
СтатьяПоддержка правительства СШАПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Chao Cara W, Sprouse Kaitlin R, Miranda Marcos C, Catanzaro Nicholas J, Hubbard Miranda L, Addetia Amin, Stewart Cameron, Brown Jack T, Dosey Annie, Valdez Adian, Ravichandran Rashmi, Hendricks Grace G, Ahlrichs Maggie, Dobbins Craig, Hand Alexis, McGowan Jackson, Simmons Boston, Treichel Catherine, Willoughby Isabelle, Walls Alexandra C, McGuire Andrew T, Leaf Elizabeth M, Baric Ralph S, Schäfer Alexandra, Veesler David, King Neil P
Аннотация
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.