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Synergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection

Author

Listed:
  • Hadas Tamir

    (Israel Institute for Biological Research)

  • Tal Noy-Porat

    (Israel Institute for Biological Research)

  • Sharon Melamed

    (Israel Institute for Biological Research)

  • Lilach Cherry-Mimran

    (Israel Institute for Biological Research)

  • Moria Barlev-Gross

    (Israel Institute for Biological Research)

  • Ron Alcalay

    (Israel Institute for Biological Research)

  • Yfat Yahalom-Ronen

    (Israel Institute for Biological Research)

  • Hagit Achdout

    (Israel Institute for Biological Research)

  • Boaz Politi

    (Israel Institute for Biological Research)

  • Noam Erez

    (Israel Institute for Biological Research)

  • Shay Weiss

    (Israel Institute for Biological Research)

  • Ronit Rosenfeld

    (Israel Institute for Biological Research)

  • Eyal Epstein

    (Israel Institute for Biological Research)

  • Ohad Mazor

    (Israel Institute for Biological Research)

  • Efi Makdasi

    (Israel Institute for Biological Research)

  • Nir Paran

    (Israel Institute for Biological Research)

  • Tomer Israely

    (Israel Institute for Biological Research)

Abstract

The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 and EV42, targeting the two infectious forms of the virus, were selected for in vivo evaluation, based on their in vitro neutralization potency. A single dose of either MV33 or EV42 administered three days post-infection (dpi) to BALB/c female mice provides full protection against lethal ectromelia virus challenge. Importantly, a combination of both mAbs confers full protection even when provided five dpi. Whole-body bioimaging and viral load analysis reveal that combination of the two mAbs allows for faster and more efficient clearance of the virus from target organs compared to either MV33 or EV42 separately. The combined mAbs treatment further confers post-exposure protection against the currently circulating Monkeypox virus in Cast/EiJ female mice, highlighting their therapeutic potential against other orthopoxviruses.

Suggested Citation

  • Hadas Tamir & Tal Noy-Porat & Sharon Melamed & Lilach Cherry-Mimran & Moria Barlev-Gross & Ron Alcalay & Yfat Yahalom-Ronen & Hagit Achdout & Boaz Politi & Noam Erez & Shay Weiss & Ronit Rosenfeld & E, 2024. "Synergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47328-y
    DOI: 10.1038/s41467-024-47328-y
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    References listed on IDEAS

    as
    1. Ronit Rosenfeld & Tal Noy-Porat & Adva Mechaly & Efi Makdasi & Yinon Levy & Ron Alcalay & Reut Falach & Moshe Aftalion & Eyal Epstein & David Gur & Theodor Chitlaru & Einat B. Vitner & Sharon Melamed , 2021. "Post-exposure protection of SARS-CoV-2 lethal infected K18-hACE2 transgenic mice by neutralizing human monoclonal antibody," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
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