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Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus

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    Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus
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    • Oscar A. Ortega-Rivera
      Oscar A. Ortega-Rivera
      Department of NanoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      More by Oscar A. Ortega-Rivera
      Orcidhttps://orcid.org/0000-0002-0773-0677
    • Sourabh Shukla
      Sourabh Shukla
      Department of NanoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      More by Sourabh Shukla
      Orcidhttps://orcid.org/0000-0001-9751-5833
    • Matthew D. Shin
      Matthew D. Shin
      Department of NanoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      More by Matthew D. Shin
    • Angela Chen
      Angela Chen
      Department of NanoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      More by Angela Chen
    • Veronique Beiss
      Veronique Beiss
      Department of NanoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      More by Veronique Beiss
    • Miguel A. Moreno-Gonzalez
      Miguel A. Moreno-Gonzalez
      Department of NanoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      More by Miguel A. Moreno-Gonzalez
      Orcidhttps://orcid.org/0000-0002-1601-9369
    • Yi Zheng
      Yi Zheng
      Department of NanoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      More by Yi Zheng
    • Alex E. Clark
      Alex E. Clark
      Department of Medicine, University of California-San Diego, La Jolla, California 92039, United States
      More by Alex E. Clark
    • Aaron F. Carlin
      Aaron F. Carlin
      Department of Medicine, University of California-San Diego, La Jolla, California 92039, United States
      More by Aaron F. Carlin
      Orcidhttps://orcid.org/0000-0002-1669-8066
    • Jonathan K. Pokorski
      Jonathan K. Pokorski
      Department of NanoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Institute for Materials Discovery and Design, University of California-San Diego, La Jolla, California 92039, United States
      More by Jonathan K. Pokorski
      Orcidhttps://orcid.org/0000-0001-5869-6942
    • Nicole F. Steinmetz*
      Nicole F. Steinmetz
      Department of NanoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Center for Nano-ImmunoEngineering, University of California-San Diego, La Jolla, California 92039, United States
      Institute for Materials Discovery and Design, University of California-San Diego, La Jolla, California 92039, United States
      Department of Bioengineering, University of California-San Diego, La Jolla, California 92039, United States
      Department of Radiology, University of California-San Diego, La Jolla, California 92039, United States
      Moores Cancer Center, University of California-San Diego, La Jolla, California 92039, United States
      *Email: [email protected]
      More by Nicole F. Steinmetz
      Orcidhttps://orcid.org/0000-0002-0130-0481
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    ACS Infectious Diseases

    Cite this: ACS Infect. Dis. 2021, 7, 11, 3096–3110
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsinfecdis.1c00410
    Published October 21, 2021
    Copyright © 2021 American Chemical Society
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    Abstract

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    The development of vaccines against coronaviruses has focused on the spike (S) protein, which is required for the recognition of host-cell receptors and thus elicits neutralizing antibodies. Targeting conserved epitopes on the S protein offers the potential for pan-beta-coronavirus vaccines that could prevent future pandemics. We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2–4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). A pentavalent slow-release implant comprising all five peptides displayed on the CPMV elicited anti-S protein and epitope-specific antibody titers, albeit at a lower magnitude compared to the soluble formulations. While the CPMV remained intact when released from the PLGA implants, processing results in loss of RNA, which acts as an adjuvant. Loss of RNA may be a reason for the lower efficacy of the implants. Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. While a cross-protective vaccine candidate was not developed, a multivalent SARS vaccine was developed. The technology discussed here is a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases.

    Copyright © 2021 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsinfecdis.1c00410.

    • Ig isotype profile (Figure S1), characterization of CPMV-Cy5 (Figure S2) and CPMV released from PLGA implants (Figure S3), and IgG titers against CPMV comparing soluble vs implant administration (Figure S4) (PDF)

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    Cited By

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    This article is cited by 20 publications.

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    ACS Infectious Diseases

    Cite this: ACS Infect. Dis. 2021, 7, 11, 3096–3110
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsinfecdis.1c00410
    Published October 21, 2021
    Copyright © 2021 American Chemical Society
    Request reuse permissions

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