TY - JOUR
T1 - Combination therapy with remdesivir and monoclonal antibodies protects nonhuman primates against advanced Sudan virus disease
AU - Cross, Robert W.
AU - Bornholdt, Zachary A.
AU - Prasad, Abhishek
AU - Woolsey, Courtney
AU - Borisevich, Viktoriya
AU - Agans, Krystle N.
AU - Deer, Daniel J.
AU - Abelson, Dafna M.
AU - Kim, Do H.
AU - Shestowsky, William S.
AU - Campbell, Lioudmila A.
AU - Bunyan, Elaine
AU - Geisbert, Joan B.
AU - Dobias, Natalie S.
AU - Fenton, Karla
AU - Porter, Danielle P.
AU - Zeitlin, Larry
AU - Geisbert, Thomas W.
N1 - Funding Information:
The authors would like to thank the UTMB Animal Resource Center for husbandry support of laboratory animals and Kevin Melody for assistance with the animal studies. This study was supported by the Department of Health and Human Services, NIH grant U19AI142785 to TWG and UC7AI094660 for BSL-4 operations support of the Galveston National Laboratory. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by UTMB. We also thank Alejandro Villasante-Tezanos from the UTMB Biostatistics Department for helpful discussions on data interpretation from this study. The graphical abstract was constructed using BioRender.com.
Publisher Copyright:
© 2022, Cross et al.
PY - 2022/5/23
Y1 - 2022/5/23
N2 - A major challenge in managing acute viral infections is ameliorating disease when treatment is delayed. Previously, we reported the success of a 2-pronged mAb and antiviral remdesivir therapeutic approach to treat advanced illness in rhesus monkeys infected with Marburg virus (MARV). Here, we explored the benefit of a similar combination therapy for Sudan ebolavirus (Sudan virus; SUDV) infection. Importantly, no licensed anti-SUDV therapeutics currently exist, and infection of rhesus macaques with SUDV results in a rapid disease course similar to MARV with a mean time to death of 8.3 days. When initiation of therapy with either remdesivir or a pan-ebolavirus mAb cocktail (MBP431) was delayed until 6 days after inoculation, only 20% of macaques survived. In contrast, when remdesivir and MBP431 treatment were combined beginning 6 days after inoculation, significant protection (80%) was achieved. Our results suggest that combination therapy may be a viable treatment for patients with advanced filovirus disease that warrants further clinical testing in future outbreaks.
AB - A major challenge in managing acute viral infections is ameliorating disease when treatment is delayed. Previously, we reported the success of a 2-pronged mAb and antiviral remdesivir therapeutic approach to treat advanced illness in rhesus monkeys infected with Marburg virus (MARV). Here, we explored the benefit of a similar combination therapy for Sudan ebolavirus (Sudan virus; SUDV) infection. Importantly, no licensed anti-SUDV therapeutics currently exist, and infection of rhesus macaques with SUDV results in a rapid disease course similar to MARV with a mean time to death of 8.3 days. When initiation of therapy with either remdesivir or a pan-ebolavirus mAb cocktail (MBP431) was delayed until 6 days after inoculation, only 20% of macaques survived. In contrast, when remdesivir and MBP431 treatment were combined beginning 6 days after inoculation, significant protection (80%) was achieved. Our results suggest that combination therapy may be a viable treatment for patients with advanced filovirus disease that warrants further clinical testing in future outbreaks.
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U2 - 10.1172/jci.insight.159090
DO - 10.1172/jci.insight.159090
M3 - Article
C2 - 35413016
AN - SCOPUS:85130723362
SN - 2379-3708
VL - 7
JO - JCI insight
JF - JCI insight
IS - 10
M1 - e159090
ER -