Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV
Cara W. Chao, Kaitlin R. Sprouse, Marcos C. Miranda, Nicholas Catanzaro, Miranda L. Hubbard, Amin Addetia, Cameron Stewart, Jack T Brown, Annie Dosey, Adian Valdez, Rashmi Ravichandran, Grace G. Hendricks, Maggie Ahlrichs, Craig L. Dobbins, Alexis Hand, Jackson McGowan, Boston Simmons, Catherine Treichel, Isabelle Willoughby, Alexandra C. Walls, Andrew T. McGuire, Elizabeth M. Leaf, Ralph S. Baric, Alexandra Schäfer, David Veesler, Neil P. King
Abstract
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.