Cell Reports (Dec 2024)
Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV
- Cara W. Chao,
- Kaitlin R. Sprouse,
- Marcos C. Miranda,
- Nicholas J. Catanzaro,
- Miranda L. Hubbard,
- Amin Addetia,
- Cameron Stewart,
- Jack T. Brown,
- Annie Dosey,
- Adian Valdez,
- Rashmi Ravichandran,
- Grace G. Hendricks,
- Maggie Ahlrichs,
- Craig 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
Affiliations
- Cara W. Chao
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USA
- Kaitlin R. Sprouse
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Marcos C. Miranda
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Nicholas J. Catanzaro
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
- Miranda L. Hubbard
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
- Amin Addetia
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Cameron Stewart
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Jack T. Brown
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Annie Dosey
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Adian Valdez
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Rashmi Ravichandran
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Grace G. Hendricks
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Maggie Ahlrichs
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Craig Dobbins
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Alexis Hand
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Jackson McGowan
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Boston Simmons
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Catherine Treichel
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Isabelle Willoughby
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Alexandra C. Walls
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Andrew T. McGuire
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle WA 98115, USA
- Elizabeth M. Leaf
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
- Ralph S. Baric
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
- Alexandra Schäfer
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
- David Veesler
- Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA
- Neil P. King
- Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Corresponding author
- Journal volume & issue
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Vol. 43,
no. 12
p. 115036
Abstract
Summary: 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.
