Marburg Virus Medical Countermeasures.

Karen A Martins, Daniel N Wolfe
Author Information
  1. Karen A Martins: Biomedical Advanced Research and Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), U.S. Department of Health and Human Services (HHS), Washington, DC, USA. karen.martins@hhs.gov.
  2. Daniel N Wolfe: Biomedical Advanced Research and Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR), U.S. Department of Health and Human Services (HHS), Washington, DC, USA.

Abstract

Among the Filoviridae, Marburg virus (MARV) is a biological threat for which no licensed vaccines or therapeutics are currently available. In contrast, we have licensed products for Ebola virus (EBOV), another member of the Filoviridae family. The availability of licensed medical countermeasures (MCMs) for EBOV provides an opportunity to test a key objective of many pandemic preparedness plans, which is to apply some of the same technological approaches demonstrated to be successful for one agent, EBOV, to a second agent, MARV. This chapter will discuss (1) lessons learned from EBOV outbreak responses and MCM development that are applicable to MARV MCM development, (2) the likely concept of operations for using vaccines and therapeutics against MARV, and (3) target product profiles based on the concept of operations. Finally, we will discuss the current status of the MCM pipeline for MARV and next steps to advance these countermeasures to licensure.

Keywords

References

  1. CDC (2023) Marburg virus disease outbreaks. 2023 [cited 2023 8/22/2023]. Available from: https://www.cdc.gov/vhf/marburg/outbreaks/chronology.html
  2. Amman BR, Bird BH, Bakarr IA, Bangura J, Schuh AJ et al (2020) Isolation of Angola-like Marburg virus from Egyptian rousette bats from West Africa. Nat Commun 11(1):510 [DOI: 10.1038/s41467-020-14327-8]
  3. Towner JS, Amman BR, Sealy TK, Reeder Carroll SA, Comer JA et al (2009) Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog 5(7):e1000536 [DOI: 10.1371/journal.ppat.1000536]
  4. Schindell BG, Webb AL, Kindrachuk J (2018) Persistence and sexual transmission of filoviruses. Viruses 10(12):683 [DOI: 10.3390/v10120683]
  5. Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M et al (2017) Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola ��a Suffit!). Lancet 389:P505���P518 [DOI: 10.1016/S0140-6736(16)32621-6]
  6. FDA (2023) Package Insert ��� ERVEBO. 2023 [cited 2023 8/21/2023]. Available from: https://www.fda.gov/media/133748/download#:~:text=ERVEBO%C2%AE%20is%20indicated%20for,months%20of%20age%20and%20older.&text=The%20duration%20of%20protection%20conferred%20by%20ERVEBO%20is%20unknown.,-%E2%80%A2&text=ERVEBO%20does%20not%20protect%20against%20other%20species%20of%20Ebolavirus%20or%20Marburgvirus.,-%E2%80%A2
  7. Garbutt M, Liebscher R, Wahl-Jensen V, Jones S, Moller P, Wagner R, Volchkov V, Klenk H, Feldmann H, Stroher U (2004) Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. J Virol 78(10):5458���5465 [DOI: 10.1128/JVI.78.10.5458-5465.2004]
  8. NIAID (2021) NIAID pandemic preparedness plan. www.niaid.nih.gov/research/pandemic-preparedness
  9. BARDA (2022) BARDA���s strategic plan 2022���2026. 2022 [cited 2023 8/21/2023]. Available from: https://medicalcountermeasures.gov/barda/strategic-plan/
  10. whitehouse.gov (2022) National Biodefense Strategy and Implementation Plan, W. House, Editor
  11. consortium, E.c.s.r.v.t (2015) The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola. BMJ 351:h3740
  12. Malenfant JH, Joyce A, Choi MJ, Cossaboom CM, Whitesell AN et al (2021) Use of Ebola vaccine: expansion of recommendations of the Advisory Committee on immunization practices to include two additional populations���United States, 2021. MMWR Morb Mortal Wkly Rep 71(8):290���292 [DOI: 10.15585/mmwr.mm7108a2]
  13. WHO (2023) WHO Technical Advisory Group ��� candidate vaccine prioritization. www.who.int/publications/m/item/marburg-virus-vaccine-landscape
  14. Mulangu S, Dodd LE, Davey RT, Mbaya OT, Proschan M et al (2019) A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med 381:2293���2303 [DOI: 10.1056/NEJMoa1910993]
  15. Martini GA (1973) Marburg virus disease. Postgrad Med J 49(574):542���546 [DOI: 10.1136/pgmj.49.574.542]
  16. Coffin KM, Liu J, Warren TK, Blancett CD, Kuehl KA et al (2018) Persistent Marburg virus infection in the testes of nonhuman primate survivors. Cell Host Microbe 24(3):405���416.e3 [DOI: 10.1016/j.chom.2018.08.003]
  17. BARDA (2023) BARDA Target Product Profiles (TPP). 2023 [cited 2023 8/24/2023]. Available from: https://medicalcountermeasures.gov/barda/tpp
  18. NIAID (2023) Target Product Profile (TPP) for APP antiviral therapeutics: Filovirus disease. 2023 [cited 2023 8/24/2023]. Available from: https://www.niaid.nih.gov/sites/default/files/filovirus-target-product-antivirals.pdf
  19. Kennedy SB, Bolay F, Kieh M, Grandits G, Badio M et al (2017) Phase 2 placebo-controlled trial of two vaccines to prevent Ebola in Liberia. N Engl J Med 377:1438���1447 [DOI: 10.1056/NEJMoa1614067]
  20. Hunegnaw R, Honko AN, Wang L, Carr D, Murray T et al (2022) A single-shot ChAd3-MARV vaccine confers rapid and durable protection against Marburg virus in nonhuman primates. Sci Transl Med 14(675):eabq6364 [DOI: 10.1126/scitranslmed.abq6364]
  21. Finch CL, King TH, Alfson KJ, Albanese KA, Smith JN et al (2022) Single-shot ChAd3-MARV vaccine in modified formulation buffer shows 100% protection of NHPs. Vaccines (Basel) 10(11):1935 [DOI: 10.3390/vaccines10111935]
  22. Hamer MJ, Houser KV, Hofstetter AR, Ortega-Villa AM, Lee C et al (2023) Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial. Lancet 401(10373):294���302 [DOI: 10.1016/S0140-6736(22)02400-X]
  23. Parish LA, Stavale EJ, Houchens CR, Wolfe DN (2023) Developing vaccines to improve preparedness for filovirus outbreaks: the perspective of the USA Biomedical Advanced Research and Development Authority (BARDA). Vaccine 11(6):1120 [DOI: 10.3390/vaccines11061120]
  24. mcm.gov (2023) BARDA continues partnership with Sabin Vaccine Institute to advance development and manufacturing of two filovirus vaccines. medicalcountermeasures.gov
  25. Voysey M, Clemens SAC, Madhi SA, Weckx L, Folegatti PM et al (2021) Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 397(10269):99���111 [DOI: 10.1016/S0140-6736(20)32661-1]
  26. Sebastian S, Flaxman A, Cha KM, Ulaszewska M, Gilbride C et al (2020) A multi-filovirus vaccine candidate: co-expression of Ebola, Sudan, and Marburg antigens in a single vector. Vaccine (Basel) 8(2):241 [DOI: 10.3390/vaccines8020241]
  27. Oxford, U.o (2023) Overview of ChAdOx1 Marburg. 2023 [cited 2023 8/24/2023]. Available from: https://cdn.who.int/media/docs/default-source/blue-print/teresa-lambe_session-1_university-of-oxford-_marvac-consultation_10-march-2023.pdf?sfvrsn=f68c9e1e_3
  28. Cooper CL, Morrow G, Yuan M, Coleman JW, Hou F et al (2022) Vaccination with a vesicular stomatitis virus vector-based vaccine prepared under conditions to allow advancement to human clinical trials. Vaccine 10(10):1582 [DOI: 10.3390/vaccines10101582]
  29. Zhu W, Liu G, Cao W, He S, Leung A et al (2022) A cloned recombinant vesicular stomatitis virus-vectored Marburg vaccine, PHV01, protects Guinea pigs from lethal Marburg virus disease. Vaccines (Basel) 10(7):1004 [DOI: 10.3390/vaccines10071004]
  30. Clarke DK, Rong X, Matassov D, Latham TE, Ota-Setlik A et al (2020) Safety and immunogenicity of a highly attenuated rVSVN4CT1-EBOVGP1 Ebola virus vaccine: a randomised, double-blind, placebo-controlled, phase 1 clinical trial. Lancet Infect Dis 20(4):455���466 [DOI: 10.1016/S1473-3099(19)30614-0]
  31. Matassov D, Mire CE, Latham T, Geisbert JB, Xu R et al (2018) Single-dose trivalent vesiculovax vaccine protects macaques from lethal ebolavirus and Marburgvirus challenge. J Virol 92(3):e01190���e01117 [DOI: 10.1128/JVI.01190-17]
  32. Woolsey C, Cross RW, Agans KN, Borisevich V, Deer DJ et al (2022) A highly attenuated Vesiculovax vaccine rapidly protects nonhuman primates against lethal Marburg virus challenge. PLoS Negl Trop Dis 16(5):e0010433 [DOI: 10.1371/journal.pntd.0010433]
  33. Bockstal V, Shukarev G, McLean C, Goldsstein N, Bart S et al (2022) First-in-human study to evaluate safety, tolerability, and immunogenicity of heterologous regimens using the multivalent filovirus vaccines Ad26.Filo and MVA-BN-Filo administered in different sequences and schedules: a randomized, controlled study. PLoS One 17(10):e0274906 [DOI: 10.1371/journal.pone.0274906]
  34. Tiemessen MM, Solforosi L, Dekking L, Czapska-Casey D, Serroyen J et al (2022) Protection against Marburg virus and Sudan virus in NHP by an adenovector-based trivalent vaccine regimen is correlated to humoral immune response levels. Vaccine (Basel) 10(8):1263 [DOI: 10.3390/vaccines10081263]
  35. Keshwara R, Hagen KR, Abreu-Mota T, Papaneri AB, Liu D et al (2019) A recombinant rabies virus expressing the Marburg virus glycoprotein is dependent upon antibody-mediated cellular cytotoxicity for protection against Marburg virus disease in a murine model. J Virol 93(6):e01865���e01818 [DOI: 10.1128/JVI.01865-18]
  36. Malherbe DC, Brian Kimble J, Atyeo C, Fischinger S, Meyer M et al (2023) A single dose intranasal combination panebolavirus vaccine. J Infect Dis 228(Suppl 7):S648���S659 [DOI: 10.1093/infdis/jiad266]
  37. Sarwar UN, Costner P, Enama ME, Berkowitz N, Hu Z et al (2014) Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase 1 clinical trial. J Infect Dis 211:549���557 [DOI: 10.1093/infdis/jiu511]
  38. Jiang J, Ramos SJ, Bangalore P, Elwood D, Cashman KA et al (2021) Multivalent DNA vaccines as a strategy to combat multiple concurrent epidemics: mosquito-borne and hemorrhagic fever viruses. Viruses 13(3):382 [DOI: 10.3390/v13030382]
  39. United STates Department of Defense (2020) DOD-funded drug remdesivir receives FDA approval for COVID-19 treatment. 2020 [cited 2023 11/19/2023]. Available from: https://www.jpeocbrnd.osd.mil/Media/News/Article/2431405/dod-funded-drug-remdesivir-receives-fda-approval-for-covid-19-treatment/
  40. FDA (2020) FDA approves first treatment for COVID-19. 2020 [cited 2023 11/19/2023]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19
  41. Hickman MR, Saunders DL, Bigger CA, Kane CD, Iversen PL (2022) The development of broad-spectrum antiviral medical countermeasures to treat viral hemorrhagic fevers caused by natural or weaponized virus infections. PLoS Negl Trop Dis 16(3):e0010220 [DOI: 10.1371/journal.pntd.0010220]
  42. Porter BP, Weidner JM, Gomba L, Bannister R, Blair C et al (2020) Remdesivir (GS-5734) is efficacious in cynomolgus macaques infected with Marburg virus. J Infect Dis 222(11):1894���1901 [DOI: 10.1093/infdis/jiaa290]
  43. Cross RW, Bornholdt ZA, Prasad AN, Borisevich V, Agans KN et al (2021) Combination therapy protects macaques against advanced Marburg virus disease. Nat Commun 12(1):1891 [DOI: 10.1038/s41467-021-22132-0]
  44. King LB, Fusco ML, Flyak AI, Ilinykh PA, Huang K et al (2018) The Marburgvirus-neutralizing human monoclonal antibody MR191 targets a conserved site to block virus receptor binding. Cell Host Microbe 23(1):101���109.e4 [DOI: 10.1016/j.chom.2017.12.003]
  45. Mire CE, Geisbert JB, Borisevich V, Fenton KA, Agans KN et al (2017) Therapeutic treatment of Marburg and Ravn virus infection in nonhuman primates with a human monoclonal antibody. Sci Transl Med 9(384):eaai8711 [DOI: 10.1126/scitranslmed.aai8711]
  46. Cross RW, Mire CE, Feldmann H, Geisbert TW (2018) Post-exposure treatments for Ebola and Marburg virus infections. Nat Rev Drug Discov 17(6):413���434 [DOI: 10.1038/nrd.2017.251]
  47. Crozier I, Britson KA, Wolfe DN, Klena JD, Hensley LE et al (2022) The evolution of medical countermeasures for Ebola virus disease: lessons learned and next steps. Vaccine (Basel) 10(8):1213 [DOI: 10.3390/vaccines10081213]
  48. FDA (2015) Product development under the animal rule guidance for industry. 2015 [cited 2023 9/1/2023]. Available from: https://www.fda.gov/media/88625/download
  49. Comer JE, Brasel T, Massey S, Beasley DW, Cirimotich CM et al (2022) Natural history of Marburg virus infection to suppor medical countermeasure development. Viruses 14(10):2291 [DOI: 10.3390/v14102291]

MeSH Term

Marburgvirus
Marburg Virus Disease
Humans
Animals
Medical Countermeasures
Hemorrhagic Fever, Ebola
Antiviral Agents
Viral Vaccines
Ebolavirus
Disease Outbreaks

Chemicals

Antiviral Agents
Viral Vaccines

Word Cloud

Created with Highcharts 10.0.0MARVEBOVlicensedMCMFiloviridaeMarburgvirusvaccinestherapeuticscountermeasuresagentwilldiscussdevelopmentconceptoperationsAmongbiologicalthreatcurrentlyavailablecontrastproductsEbolaanothermemberfamilyavailabilitymedicalMCMsprovidesopportunitytestkeyobjectivemanypandemicpreparednessplansapplytechnologicalapproachesdemonstratedsuccessfulonesecondchapter1lessonslearnedoutbreakresponsesapplicable2likelyusing3targetproductprofilesbasedFinallycurrentstatuspipelinenextstepsadvancelicensureVirusMedicalCountermeasuresAntibodiesClinicaltrialsFilovirusTherapeuticVaccine

Similar Articles

Cited By