Prior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment

Robert W. Cross; Zachary A. Bornholdt; Abhishek N. Prasad; Joan B. Geisbert; Viktoriya Borisevich; Krystle N. Agans; Daniel J. Deer; Kevin Melody; Karla A. Fenton; Heinz Feldmann; Armand Sprecher; Larry Zeitlin; Thomas W. Geisbert

doi:10.1038/s41467-020-17446-4

Prior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment

Robert W. Cross, Zachary A. Bornholdt, Abhishek N. Prasad, Joan B. Geisbert, Viktoriya Borisevich, Krystle N. Agans, Daniel J. Deer, Kevin Melody, Karla A. Fenton, Heinz Feldmann, Armand Sprecher, Larry Zeitlin, Thomas W. Geisbert

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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 epidemic. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP have shown promise in animals and humans when administered therapeutically. Uncertainty exists regarding the efficacy of postexposure antibody treatments in the event of a known exposure of a recent rVSV-ZEBOV vaccinee. Here, we model a worst-case scenario using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. We demonstrate that animals challenged with a uniformly lethal dose of EBOV one day following vaccination, and then treated with the anti-EBOV GP mAb MIL77 starting 3 days postexposure show no evidence of clinical illness and survive challenge. In contrast, animals receiving only vaccination or only mAb-based therapy become ill, with decreased survival compared to animals vaccinated and subsequently treated with MIL77. These results suggest that rVSV-ZEBOV augments immunotherapy.

Original language	English (US)
Article number	3736
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-17446-4
State	Published - Dec 1 2020

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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., Zeitlin, L., & Geisbert, T. W. (2020). Prior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment. Nature communications, 11(1), Article 3736. https://doi.org/10.1038/s41467-020-17446-4

Cross, RW, Bornholdt, ZA, Prasad, AN, Geisbert, JB, Borisevich, V, Agans, KN, Deer, DJ, Melody, K, Fenton, KA, Feldmann, H, Sprecher, A, Zeitlin, L & Geisbert, TW 2020, 'Prior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment', Nature communications, vol. 11, no. 1, 3736. https://doi.org/10.1038/s41467-020-17446-4

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title = "Prior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment",

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 epidemic. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP have shown promise in animals and humans when administered therapeutically. Uncertainty exists regarding the efficacy of postexposure antibody treatments in the event of a known exposure of a recent rVSV-ZEBOV vaccinee. Here, we model a worst-case scenario using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. We demonstrate that animals challenged with a uniformly lethal dose of EBOV one day following vaccination, and then treated with the anti-EBOV GP mAb MIL77 starting 3 days postexposure show no evidence of clinical illness and survive challenge. In contrast, animals receiving only vaccination or only mAb-based therapy become ill, with decreased survival compared to animals vaccinated and subsequently treated with MIL77. These results suggest that rVSV-ZEBOV augments immunotherapy.",

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Prior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment

Abstract

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