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Mpox multiprotein virus-like nanoparticle vaccine induces neutralizing and protective antibodies in mice and non-human primates

Author

Listed:
  • Ahmed A. Belghith

    (National Institutes of Health)

  • Catherine A. Cotter

    (National Institutes of Health)

  • Maxinne A. Ignacio

    (National Institutes of Health)

  • Patricia L. Earl

    (National Institutes of Health)

  • Rory A. Hills

    (University of Oxford
    University of Cambridge)

  • Mark R. Howarth

    (University of Cambridge)

  • Debra S. Yee

    (National Institutes of Health)

  • Jason M. Brenchley

    (National Institutes of Health)

  • Bernard Moss

    (National Institutes of Health)

Abstract

The upsurge of mpox in Africa and the recent global outbreak have stimulated the development of new vaccines and therapeutics. We describe the construction of virus-like particle (VLP) vaccines in which modified M1, A35 and B6 proteins from monkeypox virus (MPXV) clade Ia are conjugated individually or together to a scaffold that accommodates up to 60 ligands using the SpyTag/SpyCatcher nanoparticle system. Immunisation of female mice with VLPs induces higher anti-MPXV and anti-vaccinia virus (VACV) neutralizing antibodies than their soluble protein (SP) counterparts or modified VACV Ankara (MVA). Vaccination with individual single protein VLPs provides partial protection against lethal respiratory infections with VACV or MPXV clade IIa, whereas combinations or a chimeric VLP with all three antigens provide complete protection that is superior to SPs. Additionally, the VLP vaccine reduces the replication and spread of the virus at intranasal and intrarectal sites of inoculation. VLPs induce higher neutralizing activity than the Jynneos vaccine in rhesus macaques, and the VLP-induced antiserum provides better protection against MPXV and VACV than the Jynneos-induced antiserum when passively transferred to female mice. These data demonstrate that an mpox VLP vaccine derived from three MPXV clade Ia proteins protects against clade IIa MPXV and VACV, indicating cross-reactivity for orthopoxviruses.

Suggested Citation

  • Ahmed A. Belghith & Catherine A. Cotter & Maxinne A. Ignacio & Patricia L. Earl & Rory A. Hills & Mark R. Howarth & Debra S. Yee & Jason M. Brenchley & Bernard Moss, 2025. "Mpox multiprotein virus-like nanoparticle vaccine induces neutralizing and protective antibodies in mice and non-human primates," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59826-8
    DOI: 10.1038/s41467-025-59826-8
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    References listed on IDEAS

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    1. Fujun Hou & Yuntao Zhang & Xiaohu Liu & Yanal M Murad & Jiang Xu & Zhibin Yu & Xianwu Hua & Yingying Song & Jun Ding & Hongwei Huang & Ronghua Zhao & William Jia & Xiaoming Yang, 2023. "mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Tiong Kit Tan & Pramila Rijal & Rolle Rahikainen & Anthony H. Keeble & Lisa Schimanski & Saira Hussain & Ruth Harvey & Jack W. P. Hayes & Jane C. Edwards & Rebecca K. McLean & Veronica Martini & Miria, 2021. "A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
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