Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a pan-Ebolavirus Immunotherapeutic

Kuang, E.; Cross, R. W.; McCavitt-Malvido, M.; Abelson, D. M.; Borisevich, V.; Agans, K. N.; Mlakar, N.; Marimuthu, A.; Deer, D. J.; Shestowsky, W. S.; Kim, D.; Geisbert, J. B.; Zeitlin, L.; Moyer, C. L.; Roy, C. J.; Geisbert, T.; Bornholdt, Z. A.

doi:10.1101/2022.01.06.475142

bioRxiv · 10.1101/2022.01.06.475142

Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a pan-Ebolavirus Immunotherapeutic

Kuang, E.·Cross, R. W.·McCavitt-Malvido, M.·Abelson, D. M.·Borisevich, V.·Agans, K. N.·Mlakar, N.·Marimuthu, A.·Deer, D. J.·Shestowsky, W. S.·Kim, D.·Geisbert, J. B.·Zeitlin, L.·Moyer, C. L.·Roy, C. J.·Geisbert, T.·Bornholdt, Z. A.

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Abstract

Intravenous administration (IV) of antiviral monoclonal antibodies (mAbs) is challenging due to limited resources for performing infusions during an ongoing epidemic. An ebolavirus therapeutic administered via intramuscular (IM) injection would reduce these burdens and allow rapid treatment of exposed individuals during an outbreak. Here, we demonstrate how MBP134, a two mAb pan-ebolavirus cocktail, reverses the course of Sudan ebolavirus (SUDV/Gulu) disease with a single IV or IM dose in non-human primates (NHPs) as far as five days post-exposure. Furthermore, we investigated the utility of adding half-life extension mutations to the MBP134 mAbs, ultimately creating a half-life extended cocktail designated MBP431. MBP431 demonstrated an extended serum half-life in vivo and offered complete or significant protection with a single IM dose delivered as a post-exposure prophylactic (PEP) or therapeutic in NHPs challenged with EBOV. These results support the use of MBP431 as a rapidly deployable IM medical countermeasure against every known ebolavirus.

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Kuang, E., Cross, R. W., McCavitt-Malvido, M., Abelson, D. M., Borisevich, V., Agans, K. N., Mlakar, N., Marimuthu, A., Deer, D. J., Shestowsky, W. S., Kim, D., Geisbert, J. B., Zeitlin, L., Moyer, C. L., Roy, C. J., Geisbert, T., Bornholdt, Z. A.. 2022-01-06. Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a pan-Ebolavirus Immunotherapeutic. https://doi.org/10.1101/2022.01.06.475142

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