Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV
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.
Authors
- Marcos C. Miranda (ORCID: https://orcid.org/0000-0002-2839-6997)
- Jack T Brown (ORCID: https://orcid.org/0000-0002-6159-2148)
- Elizabeth M. Leaf (ORCID: https://orcid.org/0000-0002-5354-6010)
- Neil P. King (ORCID: https://orcid.org/0000-0002-2978-4692)
- Ralph Steven Baric (ORCID: https://orcid.org/0000-0001-6827-8701)
- Alexandra C. Walls (ORCID: https://orcid.org/0000-0002-9636-8330)
- Amin Addetia (ORCID: https://orcid.org/0000-0001-6703-3841)
- Kaitlin R. Sprouse (ORCID: https://orcid.org/0000-0003-0007-2226)
- Cameron Stewart (ORCID: https://orcid.org/0000-0002-2786-6256)
- Rashmi Ravichandran (ORCID: https://orcid.org/0000-0002-2630-7487)
- Andrew T. McGuire (ORCID: https://orcid.org/0000-0003-1841-6859)
- Maggie Ahlrichs (ORCID: https://orcid.org/0000-0002-4793-3890)
- Alexis Hand (ORCID: https://orcid.org/0000-0003-3150-5661)
- Grace G. Hendricks (ORCID: https://orcid.org/0009-0008-5844-1403)
- Craig L. Dobbins
- Nicholas Catanzaro (ORCID: https://orcid.org/0000-0002-0210-8440)
- Annie Dosey (ORCID: https://orcid.org/0000-0001-6858-4725)
- Catherine Treichel (ORCID: https://orcid.org/0000-0002-6024-8505)
- Blake A. Simmons (ORCID: https://orcid.org/0000-0002-1332-1810)
- David Veesler (ORCID: https://orcid.org/0000-0002-6019-8675)
- Cara W. Chao (ORCID: https://orcid.org/0009-0004-4824-6445)
- Isabelle Willoughby
- Adian Valdez
- Alexandra Schäfer
- Jackson McGowan
- Miranda L. Hubbard (ORCID: https://orcid.org/0009-0009-4041-5431)
Institutions
- University of North Carolina at Chapel Hill (US)
- Infectious Disease Research Institute (US)
- Howard Hughes Medical Institute (US)
- University of Washington (US)
- Fred Hutch Cancer Center (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.115036
- Citations
- 10
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 3.89
Funders
- National Science Foundation
- Pfizer
- University of Washington
- National Institute of Allergy and Infectious Diseases