Combination therapy with remdesivir and monoclonal antibodies protects nonhuman primates against advanced Sudan virus disease.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Source:
      Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
    • Publication Information:
      Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-
    • Subject Terms:
    • Abstract:
      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.
    • References:
      Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5034-9. (PMID: 22411795)
      JAMA. 2020 Dec 1;324(21):2165-2176. (PMID: 33165621)
      Cell Rep. 2018 Nov 6;25(6):1385-1394.e7. (PMID: 30403995)
      mBio. 2021 Jan 12;12(1):. (PMID: 33436428)
      J Infect Dis. 2007 Nov 15;196 Suppl 2:S400-3. (PMID: 17940976)
      Pathogens. 2022 Jun 07;11(6):. (PMID: 35745509)
      Nature. 2020 Sep;585(7824):273-276. (PMID: 32516797)
      J Infect Dis. 2018 Nov 22;218(suppl_5):S649-S657. (PMID: 29982696)
      Vet Pathol. 2013 Nov;50(6):1007-15. (PMID: 23558974)
      Viruses. 2021 Jul 17;13(7):. (PMID: 34372594)
      J Virol. 1999 Jul;73(7):6024-30. (PMID: 10364354)
      Nat Commun. 2021 Mar 25;12(1):1891. (PMID: 33767178)
      N Engl J Med. 2022 Feb 10;386(6):509-520. (PMID: 34914868)
      Cell Host Microbe. 2019 Jan 9;25(1):39-48.e5. (PMID: 30629917)
      Cell Host Microbe. 2019 Jan 9;25(1):49-58.e5. (PMID: 30629918)
      PLoS Pathog. 2007 Jan;3(1):e9. (PMID: 17238286)
      Lancet. 1995 May 20;345(8960):1271-4. (PMID: 7746057)
      J Infect Dis. 1999 Feb;179 Suppl 1:S224-34. (PMID: 9988188)
      J Virol. 2009 Jul;83(14):7296-304. (PMID: 19386702)
      N Engl J Med. 2021 Dec 2;385(23):e81. (PMID: 34587383)
      Science. 2020 Aug 21;369(6506):1014-1018. (PMID: 32540904)
      J Biol Chem. 2020 Nov 20;295(47):16156-16165. (PMID: 32967965)
      Viruses. 2019 Apr 04;11(4):. (PMID: 30987343)
      Open Forum Infect Dis. 2021 Jul 06;8(11):ofab358. (PMID: 34796244)
      N Engl J Med. 2021 Nov 18;385(21):1941-1950. (PMID: 34706189)
      J Infect Dis. 1999 Feb;179 Suppl 1:S235-9. (PMID: 9988189)
      Proc Natl Acad Sci U S A. 2020 Feb 18;117(7):3768-3778. (PMID: 32015126)
      Dermatol Clin. 2004 Jul;22(3):291-302, vi. (PMID: 15207310)
      Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6771-6776. (PMID: 32054787)
      N Engl J Med. 2020 Nov 19;383(21):2030-2040. (PMID: 33031652)
      J Infect Dis. 2020 Nov 9;222(11):1894-1901. (PMID: 32479636)
      N Engl J Med. 2019 Dec 12;381(24):2293-2303. (PMID: 31774950)
      PLoS Pathog. 2009 Jul;5(7):e1000536. (PMID: 19649327)
      N Engl J Med. 2016 Oct 13;375(15):1448-1456. (PMID: 27732819)
      Lancet. 1977 Mar 12;1(8011):571-3. (PMID: 65662)
      N Engl J Med. 2015 Jun 18;372(25):2423-7. (PMID: 25950269)
      Nat Microbiol. 2017 Jul 17;2:17113. (PMID: 28715405)
      Am J Pathol. 2020 Sep;190(9):1867-1880. (PMID: 32479821)
      Nature. 2016 Mar 17;531(7594):381-5. (PMID: 26934220)
      PLoS One. 2021 Apr 28;16(4):e0250780. (PMID: 33909660)
      Virology (Auckl). 2019 Jun 21;10:1178122X19849927. (PMID: 31258326)
      Cell Host Microbe. 2018 Sep 12;24(3):405-416.e3. (PMID: 30173956)
      Arch Virol Suppl. 1996;11:135-40. (PMID: 8800795)
      Sci Transl Med. 2019 May 29;11(494):. (PMID: 31142680)
      Nat Commun. 2019 Jan 10;10(1):105. (PMID: 30631063)
      Lancet Infect Dis. 2017 May;17(5):545-552. (PMID: 28094208)
      J Virol. 2002 Jun;76(12):6408-12. (PMID: 12021376)
      J Med Virol. 2021 Dec;93(12):6737-6749. (PMID: 34370328)
      N Engl J Med. 2021 Oct 7;385(15):1382-1392. (PMID: 34260849)
      Nat Microbiol. 2016 Aug 22;1(10):16142. (PMID: 27670117)
      Nat Rev Drug Discov. 2018 Jun;17(6):413-434. (PMID: 29375139)
      N Engl J Med. 2020 Nov 5;383(19):1813-1826. (PMID: 32445440)
      Clin Microbiol Infect. 2021 Dec;27(12):1826-1837. (PMID: 34048876)
      J Infect Dis. 1999 Feb;179 Suppl 1:S48-53. (PMID: 9988164)
    • Grant Information:
      U19 AI142785 United States AI NIAID NIH HHS; UC7 AI094660 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: Immunotherapy; Virology
    • Accession Number:
      0 (Antibodies, Monoclonal)
      0 (Antibodies, Viral)
      3QKI37EEHE (remdesivir)
      415SHH325A (Adenosine Monophosphate)
      OF5P57N2ZX (Alanine)
    • Publication Date:
      Date Created: 20220412 Date Completed: 20220524 Latest Revision: 20240830
    • Publication Date:
      20240830
    • Accession Number:
      PMC9220838
    • Accession Number:
      10.1172/jci.insight.159090
    • Accession Number:
      35413016