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

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, Eyal Epstein, Ohad Mazor, Efi Makdasi, Nir Paran and Tomer Israely ()
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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

Nature Communications, 2024, vol. 15, issue 1, 1-10

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47328-y

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