Two-antibody pan-ebolavirus cocktail confers broad therapeutic protection in ferrets and nonhuman primates

Bornholdt, Z. A.; Herbert, A. S.; Mire, C. E.; He, S.; Cross, R. W.; Wec, A. Z.; Abelson, D. M.; Geisbert, J. B.; James, R. M.; Rahim, M. N.; Zhu, W.; Borisevich, V.; Banadyga, L.; Gunn, B. M.; Agans, K. N.; Goodwin, E.; Tierney, K.; Shestowsky, W. S.; Bohorov, O.; Bohorova, N.; Velasco, J.; Ailor, E.; Kim, D. H.; Pauly, M. H.; Whaley, K. J.; Alter, G.; Walker, L. M.; Chandran, K.; Zeitlin, L.; Qiu, X.; Geisbert, T. W.; Dye, J. M.

doi:10.1101/395533

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bioRxiv · 10.1101/395533

Two-antibody pan-ebolavirus cocktail confers broad therapeutic protection in ferrets and nonhuman primates

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Abstract

All available experimental vaccines and immunotherapeutics1,2 against Ebola virus (EBOV), including rVSV-ZEBOV3 and ZMappTM4, lack activity against other ebolaviruses associated with human disease outbreaks. This year, two separate outbreaks of EBOV in the Democratic Republic of Congo underscored the unpredictable nature of ebolavirus reemergence in a region that has historically experienced outbreaks of the divergent ebolaviruses Sudan virus (SUDV) and Bundibugyo virus (BDBV)5. Here we show that MBP134AF, a pan-ebolavirus therapeutic comprising two broadly neutralizing human antibodies (bNAbs)6,7(see companion manuscript, Wec et al.) could protect against lethal EBOV, SUDV, and BDBV infection in ferrets and nonhuman primates (NHPs). MBP134AF not only not only establishes a viable therapeutic countermeasure to outbreaks caused by antigenically diverse ebolaviruses but also affords unprecedented effectiveness and potency--a single 25-mg/kg dose was fully protective in NHPs. This best-in-class antibody cocktail is the culmination of an intensive collaboration spanning academia, industry and government in response to the 2013-2016 EBOV epidemic6,7 and provides a translational research model for the rapid development of immunotherapeutics targeting emerging infectious diseases.

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Bornholdt, Z. A., Herbert, A. S., Mire, C. E., He, S., Cross, R. W., Wec, A. Z., Abelson, D. M., Geisbert, J. B., James, R. M., Rahim, M. N., Zhu, W., Borisevich, V., Banadyga, L., Gunn, B. M., Agans, K. N., Goodwin, E., Tierney, K., Shestowsky, W. S., Bohorov, O., Bohorova, N., Velasco, J., Ailor, E., Kim, D. H., Pauly, M. H., Whaley, K. J., Alter, G., Walker, L. M., Chandran, K., Zeitlin, L., Qiu, X., Geisbert, T. W., Dye, J. M.. 2018-08-19. Two-antibody pan-ebolavirus cocktail confers broad therapeutic protection in ferrets and nonhuman primates. https://doi.org/10.1101/395533

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