Prior vaccination with the rVSV-ZEBOV vaccine does not interfere with but improves the efficacy of postexposure antibody treatment in nonhuman primates exposed to Ebola virus

Cross, R. W.; Bornholdt, Z. A.; Prasad, A. N.; Geisbert, J. B.; Borisevich, V.; Agans, K. N.; Deer, D. J.; Melody, K.; Fenton, K. A.; Feldmann, H.; Sprecher, A.; Geisbert, T. W.

doi:10.1101/2020.04.01.018275

bioRxiv · 10.1101/2020.04.01.018275

Prior vaccination with the rVSV-ZEBOV vaccine does not interfere with but improves the efficacy of postexposure antibody treatment in nonhuman primates exposed to Ebola virus

Cross, R. W.·Bornholdt, Z. A.·Prasad, A. N.·Geisbert, J. B.·Borisevich, V.·Agans, K. N.·Deer, D. J.·Melody, K.·Fenton, K. A.·Feldmann, H.·Sprecher, A.·Geisbert, T. W.

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Abstract

A replication-competent, vesicular stomatitis virus vaccine expressing the Ebola virus (EBOV) glycoprotein (GP) (rVSV-ZEBOV) was successfully used during the 2013-16 EBOV epidemic1. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP showed promise in animals and EBOV patients when administered therapeutically2-6. Given the large number of at-risk humans being prophylactically vaccinated with rVSV-ZEBOV, there is uncertainty regarding whether vaccination would preclude use of antibody treatments in the event of a known exposure of a recent vaccinee. To model a worst-case scenario, we performed a study using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. One day after vaccination, animals were challenged with a uniformly lethal dose of EBOV. Five vaccinated animals and five unvaccinated animals were then treated with the anti-EBOV GP mAb-based therapeutic MIL77 starting 3 days postexposure. Additionally, five vaccinated macaques received no therapeutic intervention. All five macaques that were vaccinated and subsequently treated with MIL77 showed no evidence of clinical illness and survived challenge. In contrast, all five animals that only received the rVSV-ZEBOV vaccine became ill and 2/5 survived; all five macaques that only received MIL77 only also became ill and 4/5 survived. Enhanced efficacy of vaccinated animals that were treated with MIL77 was associated with delayed EBOV viremia attributed to the vaccine. These results suggest that rVSV-ZEBOV augments immunotherapy.

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Cross, R. W., Bornholdt, Z. A., Prasad, A. N., Geisbert, J. B., Borisevich, V., Agans, K. N., Deer, D. J., Melody, K., Fenton, K. A., Feldmann, H., Sprecher, A., Geisbert, T. W.. 2020-04-02. Prior vaccination with the rVSV-ZEBOV vaccine does not interfere with but improves the efficacy of postexposure antibody treatment in nonhuman primates exposed to Ebola virus. https://doi.org/10.1101/2020.04.01.018275

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