Ebola Virus Infection: Overview and Update on Prevention and Treatment

Infectious Diseases and Therapy

Volumn 4, Issue 4, 2015, Pages 365-390

  Martínez, Miguel J ^a,b   Salim, Abdulbaset M ^c   Hurtado, Juan C ^a   Kilgore, Paul E ^c,d  

^a UNIVERSITY OF BARCELONA   (Spain)

^b CENTRE FOR RESEARCH IN ENVIRONMENTAL EPIDEMIOLOGY CREAL   (Spain)

^c WAYNE STATE UNIVERSITY   (United States)

^d WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Africa; Anti viral; EBOV; EVD; Hemorrhagic fever; Immunization; Treatment; Vaccine

Indexed keywords

ANTIDIARRHEAL AGENT; ANTIEMETIC AGENT; AVI 6002; AVI 6003; CEFOTAXIME; CEFTRIAXONE; FAVIPIRAVIR; ORAL REHYDRATION SOLUTION; SMALL INTERFERING RNA; TKM 100802; UNCLASSIFIED DRUG; VACCINE; ZMAPP;

BLOOD TRANSFUSION; CLINICAL FEATURE; DISEASE CONTROL; DISEASE TRANSMISSION; EBOLA HEMORRHAGIC FEVER; EBOLAVIRUS; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; IMMUNOTHERAPY; NUTRITION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PUBLIC HEALTH; RANDOMIZED CONTROLLED TRIAL (TOPIC); REHYDRATION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; VIROLOGY;

EID: 84977070325     PISSN: 21938229     EISSN: 21936382     Source Type: Journal    
DOI: 10.1007/s40121-015-0079-5     Document Type: Review

References (158)

1. Chowell G, Nishiura H. Characterizing the transmission dynamics and control of Ebola virus disease. PLoS Biol. 2015;13(1):e1002057.
2. Centers for Disease Control and Prevention. Ebola (Ebola virus disease), outbreaks chronology: Ebola virus disease. 2015. http://www.cdc.gov/vhf/ebola/outbreaks/history/chronology.html. Accessed 07 May 2015.
3. Hewlett BS, Amola RP. Cultural contexts of Ebola in northern Uganda. Emerg Infect Dis. 2003;9(10):1242.
4. Pandey A, et al. Strategies for containing Ebola in West Africa. Science. 2014;346(6212):991–5.
5. Kilgore PE, et al. Treatment of Ebola virus disease. Pharmacother J Hum Pharmacol Drug Ther. 2015;35(1):43–53.
6. Yazdanpanah Y, Arribas JR, Malvy D. Treatment of Ebola virus disease. Intensive Care Med. 2015;41(1):115–7.
7. Weik M, et al. The Ebola virus genomic replication promoter is bipartite and follows the rule of six. J Virol. 2005;79(16):10660–71.
8. Fauquet CM, et al. Virus taxonomy: VIIIth report of the International Committee on Taxonomy of Viruses. Academic Press; 2005.
9. Kuhn JH, et al. Proposal for a revised taxonomy of the family Filoviridae: classification, names of taxa and viruses, and virus abbreviations. Arch Virol. 2010;155(12):2083–103.
10. Kuhn JH, et al. Virus nomenclature below the species level: a standardized nomenclature for laboratory animal-adapted strains and variants of viruses assigned to the family Filoviridae. Arch Virol. 2013;158(6):1425–32.
11. Kuhn JH, et al. Virus nomenclature below the species level: a standardized nomenclature for filovirus strains and variants rescued from cDNA. Arch Virol. 2014;159(5):1229–37.
12. Negredo A, et al. Discovery of an Ebolavirus-like filovirus in Europe. PLoS Pathog. 2011;7(10):e1002304.
13. Baize S, et al. Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med. 2014;371(15):1418–25.
14. Feldmann H, Klenk HD, Sanchez A. Molecular biology and evolution of filoviruses. Arch Virol Suppl. 1993;7:81–100.
15. Sanchez A. Ebola viruses. 2003. Available from: http://onlinelibrary.wiley.com/doi/10.1038/npg.els.0001019/full. Accessed 23 July 2015.
16. Gire SK, et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science. 2014;345(6202):1369–72.
17. Haeussler M, et al. The UCSC Ebola genome portal. PLoS Curr. 2014;6. doi:10.1371/currents.outbreaks.386ab0964ab4d6c8cb550bfb6071d822.
18. Bahcall O. Ebola genomes track virus evolution in real-time epidemic. Nat Genet. 2014;46(10):1050-1050.
19. Becquart P, et al. Identification of continuous human B-cell epitopes in the VP35, VP40, nucleoprotein and glycoprotein of Ebola virus. PLoS One. 2014;9(6):e96360.
20. Watt A, et al. A novel life cycle modeling system for Ebola virus shows a genome length-dependent role of VP24 in virus infectivity. J Virol. 2014;88(18):10511–24.
21. Schieffelin JS, et al. Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med. 2014;371(22):2092–100.
22. Kugelman JR, et al. Evaluation of the potential impact of Ebola virus genomic drift on the efficacy of sequence-based candidate therapeutics. MBio. 2015;6(1):e02227–14.
23. Hoenen T, et al. Virology. Mutation rate and genotype variation of Ebola virus from Mali case sequences. Science. 2015;348(6230):117–9.
24. World Health Organization. Communicable Disease Surveillance and Response-Global Alert and Response (GAR). 2015. http://www.who.int/csr/don/en/. Accessed 15 June 2015.
25. Centers for Disease Control and Prevention. Ebola (Ebola virus disease): Ebola outbreaks 2000–2014. 2015. http://www.cdc.gov/vhf/ebola/outbreaks/history/summaries.html. Accessed 08 June 2015.
26. Centers for Disease Control and Prevention. Ebola (Ebola virus disease), 2014 Ebola outbreak in West Africa—case counts. 2015. http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html. Accessed 17 June 2015.
27. World Health Organization. Ebola situation report—8 July 2015. 2015. http://apps.who.int/ebola/current-situation/ebola-situation-report-8-july-2015. Accessed 21 July 2015.
28. Towner JS, et al. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog. 2009;5(7):e1000536.
29. Towner JS, et al. Marburg virus infection detected in a common African bat. PLoS One. 2007;2(8):e764.
30. Pourrut X, et al. Large serological survey showing cocirculation of Ebola and Marburg viruses in Gabonese bat populations, and a high seroprevalence of both viruses in Rousettus aegyptiacus. BMC Infect Dis. 2009;9:159.
31. Leroy EM, et al. Human Ebola outbreak resulting from direct exposure to fruit bats in Luebo, Democratic Republic of Congo, 2007. Vector Borne Zoonotic Dis. 2009;9(6):723–8.
32. Leroy EM, et al. Fruit bats as reservoirs of Ebola virus. Nature. 2005;438(7068):575–6.
33. Kuzmin IV, et al. Marburg virus in fruit bat, Kenya. Emerg Infect Dis. 2010;16(2):352–4.
34. Hayman DT, et al. Ebola virus antibodies in fruit bats, Ghana, West Africa. Emerg Infect Dis. 2012;18(7):1207–9.
35. Pourrut X, et al. Spatial and temporal patterns of Zaire ebolavirus antibody prevalence in the possible reservoir bat species. J Infect Dis. 2007;196(Suppl 2):S176–83.
36. Bausch DG, et al. Assessment of the risk of Ebola virus transmission from bodily fluids and fomites. J Infect Dis. 2007;196(Suppl 2):S142–7.
37. Kreuels B, et al. A case of severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2014;371(25):2394–401.
38. Rogstad KE, Tunbridge A. Ebola virus as a sexually transmitted infection. Curr Opin Infect Dis. 2015;28(1):83–5.
39. Ergonul O, Battal I. Potential sexual transmission of Crimean-Congo hemorrhagic fever infection. Jpn J Infect Dis. 2014;67(2):137–8.
40. Moreau M, et al. Lactating mothers infected with Ebola virus: EBOV RT-PCR of blood only may be insufficient. Euro Surveill. 2015;20(3). http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21017
41. Rowe AK, et al. Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidemies a Kikwit. J Infect Dis. 1999;179(Suppl 1):S28–35.
42. Shaw M, Palese P. Fields Virology. Philadelphia, PA: Lippincott Williams & Wilkins; 2013. p. 1151–1185
43. Varkey JB, et al. Persistence of Ebola virus in ocular fluid during convalescence. N Engl J Med. 2015;372(25):2423–2427.
44. World Health Organization Ebola Response Team. Ebola virus disease in West Africa—the first 9 months of the epidemic and forward projections. N Engl J Med. 2014;371(16):1481–95.
45. Breman JG, Johnson KM. Ebola then and now. N Engl J Med. 2014;371(18):1663–6.
46. Bah EI, et al. Clinical presentation of patients with Ebola virus disease in Conakry, Guinea. N Engl J Med. 2015;372(1):40–7.
47. Tattevin P, Durante-Mangoni E, Massaquoi M. Does this patient have Ebola virus disease? Intensive Care Med. 2014;40(11):1738–41.
48. Kortepeter MG, Bausch DG, Bray M. Basic clinical and laboratory features of filoviral hemorrhagic fever. J Infect Dis. 2011;204(Suppl 3):S810–6.
49. Chertow DS, et al. Ebola virus disease in West Africa—clinical manifestations and management. N Engl J Med. 2014;371(22):2054–7.
50. Fowler RA, et al. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am J Respir Crit Care Med. 2014;190(7):733–7.
51. Bwaka MA, et al. Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis. 1999;179(Suppl 1):S1–7.
52. Barry M, et al. Clinical predictors of mortality in patients with Ebola virus disease. Clin Infect Dis. 2015;60(12):1821–1824.
53. Qin E, et al. Clinical features of patients with Ebola virus disease in Sierra Leone. Clin Infect Dis. 2015;61(4):491–495. doi:10.1093/cid/civ319
54. Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011;377(9768):849–62.
55. Jaax NK, et al. Lethal experimental infection of rhesus monkeys with Ebola-Zaire (Mayinga) virus by the oral and conjunctival route of exposure. Arch Pathol Lab Med. 1996;120(2):140–55.
56. Rollin PE, Bausch DG, Sanchez A. Blood chemistry measurements and D-Dimer levels associated with fatal and nonfatal outcomes in humans infected with Sudan Ebola virus. J Infect Dis. 2007;196(Suppl 2):S364–71.
57. Centers for Disease Control and Prevention. Ebola (Ebola virus disease), guidance for collection, transport and submission of specimens for Ebola virus testing. 2015. http://www.cdc.gov/vhf/ebola/healthcare-us/laboratories/specimens.html. Accessed 14 May 2015.
58. World Health Organization. Laboratory diagnosis of Ebola virus disease. 2014. http://apps.who.int/iris/bitstream/10665/134009/1/WHO_EVD_GUIDANCE_LAB_14.1_eng.pdf?ua=1. Accessed 14 May 2015.
59. Martin P, et al. Laboratory diagnosis of Ebola virus disease. Intensive Care Med. 2015;41(5):895–8.
60. Vogel G. Infectious diseases. Testing new Ebola tests. Science. 2014;345(6204):1549–50.
61. Perkins MD, Kessel M. What Ebola tells us about outbreak diagnostic readiness. Nat Biotechnol. 2015;33(5):464–9.
62. Ksiazek TG, et al. Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis. 1999;179(Suppl 1):S177–87.
63. Leroy EM, et al. Diagnosis of Ebola haemorrhagic fever by RT-PCR in an epidemic setting. J Med Virol. 2000;60(4):463–7.
64. Towner JS, et al. Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome. J Virol. 2004;78(8):4330–41.
65. Grolla A, et al. Laboratory diagnosis of Ebola and Marburg hemorrhagic fever. Bull Soc Pathol Exot. 2005;98(3):205–9.
66. Centers for Disease Control and Prevention. Guidance for collection, transport, and submission of specimens for Ebola virus testing in the United States. 2015. http://www.cdc.gov/vhf/ebola/pdf/ebola-lab-guidance.pdf. Accessed 27 Feb 2015.
67. Kumar VS, Webster M. Extreme PCR: a breakthrough innovation for outbreaks? Clin Chem. 2015;61(4):674–6.
68. Inglis T. Developed nations must not fear sending Ebola help. Nature. 2014;514(7524):537.
69. Kaasik-Aaslav K, Coulombier D. The tail of the epidemic and the challenge of tracing the very last Ebola case. Euro surveill. 2015;20(12).
70. Walker NF, et al. Evaluation of a point-of-care blood test for identification of Ebola virus disease at Ebola holding units, Western Area, Sierra Leone, January to February 2015. Euro Surveill. 2015;20(12). http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21073.
71. Broadhurst MJ, et al. ReEBOV Antigen Rapid Test kit for point-of-care and laboratory-based testing for Ebola virus disease: a field validation study. Lancet, 2015. doi:10.1016/S0140-6736(15)61042-X.
72. Plachouras D, Monnet DL, Catchpole M. Severe Ebola virus infection complicated by gram-negative septicemia. N Engl J Med. 2015;372(14):1376–7.
73. O’Shea MK, Clay KA, Craig DG, Matthews SW, Kao RL, Fletcher TE, et al. Diagnosis of febrile illnesses other than Ebola virus disease at an Ebola treatment unit in Sierra Leone. Clin Infect Dis. 2015;61(5):795–8. doi:10.1093/cid/civ399.
74. Geisbert TW, et al. Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study. Lancet. 2010;375(9729):1896–905.
75. Thi EP, et al. Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates. Nature. 2015;521(7552):362–5.
76. Geisbert TW. Emergency treatment for exposure to Ebola virus: the need to fast-track promising vaccines. JAMA. 2015;313(12):1221–2.
77. McCarthy M. FDA allows second experimental drug to be tested in Ebola patients. BMJ. 2014;349:g5103.
78. Maurice J. WHO meeting chooses untried interventions to defeat Ebola. Lancet. 2014;384(9948):e45–6.
79. Tekmira Pharmaceuticals Corporation. Tekmira provides update on TKM-Ebola-Guinea. 2015. http://investor.tekmirapharm.com/releasedetail.cfm?ReleaseID=918694. Accessed 23 July 2015.
80. Heald AE, et al. Safety and pharmacokinetic profiles of phosphorodiamidate morpholino oligomers with activity against Ebola virus and Marburg virus: results of two single-ascending-dose studies. Antimicrob Agents Chemother. 2014;58(11):6639–47.
81. De Clercq E. Ebola virus (EBOV) infection: therapeutic strategies. Biochem Pharmacol. 2015;93(1):1–10.
82. Iversen PL, et al. Discovery and early development of AVI-7537 and AVI-7288 for the treatment of Ebola virus and Marburg virus infections. Viruses. 2012;4(11):2806–30.
83. Arias A, Thorne L, Goodfellow I. Favipiravir elicits antiviral mutagenesis during virus replication in vivo. Elife. 2014;3:e03679.
84. Furuta Y, et al. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antivir Res. 2013;100(2):446–54.
85. Gowen BB, et al. In vitro and in vivo activities of T-705 against arenavirus and bunyavirus infections. Antimicrob Agents Chemother. 2007;51(9):3168–76.
86. Safronetz D, et al. Antiviral efficacy of favipiravir against two prominent etiological agents of hantavirus pulmonary syndrome. Antimicrob Agents Chemother. 2013;57(10):4673–80.
87. Rocha-Pereira J, et al. Favipiravir (T-705) inhibits in vitro norovirus replication. Biochem Biophys Res Commun. 2012;424(4):777–80.
88. Morrey JD, et al. Efficacy of orally administered T-705 pyrazine analog on lethal West Nile virus infection in rodents. Antivir Res. 2008;80(3):377–9.
89. Oestereich L, et al. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res. 2014;105:17–21.
90. Smither SJ, et al. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model. Antivir Res. 2014;104:153–5.
91. ClinicalTrials.gov. Efficacy of Favipiravir against Ebola (JIKI). 2015. https://clinicaltrials.gov/ct2/show/NCT02329054?term=favipiravir&rank=5. Accessed 27 May 2015.
92. World Health Organization. International Clinical Trials Registry Platform. 2015. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02329054. Accessed 24 July 2015.
93. Mentre F, et al. Dose regimen of favipiravir for Ebola virus disease. Lancet Infect Dis. 2015;15(2):150–1.
94. FRANCE 24. French MSF nurse ‘cured’ of Ebola, health minister says. 2014. http://www.france24.com/en/20141004-french-nurse-cured-ebola-health-minister-msf-touraine. Accessed 09 June 2015.
95. Warren TK, et al. Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430. Nature. 2014;508(7496):402–5.
96. Falzarano D, Feldmann H. Possible leap ahead in filovirus therapeutics. Cell Res. 2014;24(6):647–8.
97. Price NB, Prichard MN. Progress in the development of new therapies for herpesvirus infections. Curr Opin Virol. 2011;1(6):548–54.
98. Florescu DF, Keck MA. Development of CMX001 (Brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses. Expert Rev Anti Infect Ther. 2014;12(10):1171–8.
99. Chimerix I. Brincidofovir for Ebola. 2015. http://www.chimerix.com/discovery-clinical-trials/brincidofovir/brincidofovir-for-ebola/. Accessed 03 Jan 2015.
100. Forbes. Chimerix ends Brincidofovir Ebola trials to focus on Adenovirus and CMV. 2015. http://www.forbes.com/sites/davidkroll/2015/01/31/chimerix-ends-brincidofovir-ebola-trials-to-focus-on-adenovirus-and-cmv/. Accessed 23 July 2015.
101. Basu A, et al. Identification of a small-molecule entry inhibitor for filoviruses. J Virol. 2011;85(7):3106–19.
102. Panchal RG, et al. Identification of an antioxidant small-molecule with broad-spectrum antiviral activity. Antiviral Res. 2012;93(1):23–9.
103. Wolf MC, et al. A broad-spectrum antiviral targeting entry of enveloped viruses. Proc Natl Acad Sci USA. 2010;107(7):3157–62.
104. Aman MJ, et al. Development of a broad-spectrum antiviral with activity against Ebola virus. Antiviral Res. 2009;83(3):245–51.
105. Warren TK, et al. Antiviral activity of a small-molecule inhibitor of filovirus infection. Antimicrob Agents Chemother. 2010;54(5):2152–9.
106. Kinch MS, et al. FGI-104: a broad-spectrum small molecule inhibitor of viral infection. Am J Transl Res. 2009;1(1):87–98.
107. Carette JE, et al. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature. 2011;477(7364):340–3.
108. Cote M, et al. Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection. Nature. 2011;477(7364):344–8.
109. Shoemaker CJ, et al. Multiple cationic amphiphiles induce a Niemann-Pick C phenotype and inhibit Ebola virus entry and infection. Plos one. 2013;8(2):e56265. doi:10.1371/journal.pone.0056265.
110. Johansen LM, et al. FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection. Science Transl Med. 2013;5(190):190ra79-190ra79.
111. Gehring G, et al. The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry. J Antimicrob Chemother. 2014;69(8):2123–31.
112. Clinicaltrials.gov. Clinical study to assess efficacy and safety of Amiodarone in treating patients with Ebola. Virus disease (EVD) in Sierra Leone. EASE (EMERGENCY Amiodarone Study Against Ebola). 2015. https://clinicaltrials.gov/ct2/results?term=NCT02307591+&Search=Search. Accessed 13 June 2015.
113. Mupapa K, et al. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee. J Infect Dis. 1999;179(Suppl 1):S18–23.
114. Colebunders RL, Cannon RO. Large-scale convalescent blood and plasma transfusion therapy for Ebola virus disease. J Infect Dis. 2015;211(8):1208–10.
115. Jahrling PB, et al. Ebola hemorrhagic fever: evaluation of passive immunotherapy in nonhuman primates. J Infect Dis. 2007;196(Suppl 2):S400–3.
116. Dye JM, et al. Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease. Proc Natl Acad Sci USA. 2012;109(13):5034–9.
117. Clinicaltrials.gov. Emergency evaluation of convalescent plasma for Ebola viral disease (EVD) in Guinea (Ebola-Tx). 2015. https://clinicaltrials.gov/ct2/show/NCT02342171?term=NCT02342171&rank=1. Accessed 13 June 2015.
118. World Health Organization. Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an emprical treatment during outbreaks. 2014. http://www.searo.who.int/entity/emerging_diseases/ebola/who_his_sds_2014.8_eng.pdf. Accessed 01 June 2015.
119. Gulland A. First Ebola treatment is approved by WHO. BMJ. 2014;349:g5539.
120. WHO Blood Regulators Network (BRN). Position paper on collection and use of convalescent plasma or serum as an element in filovirus outbreak response. Geneva: WHO; 2014.
121. Mora-Rillo M, et al. Acute respiratory distress syndrome after convalescent plasma use: treatment of a patient with Ebola virus disease contracted in Madrid, Spain. Lancet Respir Med. 2015. doi:10.1016/S2213-2600(15)00180-0
122. Takada A, et al. Antibody-dependent enhancement of Ebola virus infection. J Virol. 2003;77(13):7539–44.
123. Li H, et al. Development of therapeutics for treatment of Ebola virus infection. Microbes Infect. 2015;17(2):109–17.
124. Hernandez H, et al. Development and characterization of broadly cross-reactive monoclonal antibodies against all known Ebolavirus species. J Infect Dis. 2015. doi:10.1093/infdis/jiv209.
125. Olinger GG Jr, et al. Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques. Proc Natl Acad Sci USA. 2012;109(44):18030–5.
126. Bishop BM. Potential and emerging treatment options for Ebola virus disease. Ann Pharmacother. 2015;49(2):196–206.
127. Yu JS, et al. Anti-Ebola MAb 17A3 reacts with bovine and human alpha-2-macroglobulin proteins. J Virol Methods. 2010;168(1–2):248–50.
128. Audet J, et al. Molecular characterization of the monoclonal antibodies composing ZMAb: a protective cocktail against Ebola virus. Sci Rep. 2014;4:6881.
129. Qiu X, et al. Successful treatment of ebola virus-infected cynomolgus macaques with monoclonal antibodies. Sci Transl Med. 2012;4(138):138ra81.
130. Qiu X, et al. Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb. Sci Rep. 2013;3:3365.
131. Qiu X, et al. mAbs and Ad-vectored IFN-alpha therapy rescue Ebola-infected nonhuman primates when administered after the detection of viremia and symptoms. Sci Transl Med. 2013;5(207):207ra143.
132. Qiu X, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014;514(7520):47–53.
133. Lyon GM, et al. Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med. 2014;371(25):2402–9.
134. Giritch A, et al. Rapid high-yield expression of full-size IgG antibodies in plants coinfected with noncompeting viral vectors. Proc Natl Acad Sci USA. 2006;103(40):14701–6.
135. Zhang Y, et al. Fighting Ebola with ZMapp: spotlight on plant-made antibody. Sci China Life Sci. 2014;57(10):987–8.
136. ClinicalTrials.gov. Putative investigational therapeutics in the treatment of patients with known Ebola infection. 2015. https://clinicaltrials.gov/ct2/show/NCT02363322?term=zmapp&rank=1. Accessed 27 May 2015.
137. Wong G, Kobinger GP, Qiu X. Characterization of host immune responses in Ebola virus infections. Expert Rev Clin Immunol. 2014;10(6):781–90.
138. Cardenas WB. Evasion of the interferon-mediated antiviral response by filoviruses. Viruses. 2010;2(1):262–82.
139. Kuhl A, Pohlmann S. How Ebola virus counters the interferon system. Zoonoses Public Health. 2012;59(Suppl 2):116–31.
140. Jahrling PB, et al. Evaluation of immune globulin and recombinant interferon-alpha2b for treatment of experimental Ebola virus infections. J Infect Dis. 1999;179(Suppl 1):S224–34.
141. Smith LM, et al. Interferon-beta therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever. J Infect Dis. 2013;208(2):310–8.
142. Ansari AA. Clinical features and pathobiology of Ebolavirus infection. J Autoimmun. 2014;55:1–9.
143. Geisbert TW, et al. Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet. 2003;362(9400):1953–8.
144. Hensley LE, et al. Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever. J Infect Dis. 2007;196(Suppl 2):S390–9.
145. Business Wire. ARCA biopharma receives FDA orphan drug designation for rNAPc2 as a potential treatment for Ebola. 2014. http://www.businesswire.com/news/home/20141210005243/en/ARCA-biopharma-Receives-FDA-Orphan-Drug-Designation#.VYIkWmOuTzI. Accessed 17 June 2015.
146. Marzi A, Feldmann H. Ebola virus vaccines: an overview of current approaches. Expert Rev Vaccines. 2014;13(4):521–31.
147. Geisbert TW, et al. Evaluation in nonhuman primates of vaccines against Ebola virus. Emerg Infect Dis. 2002;8(5):503–7.
148. Martinez MJ, et al. Role of VP30 phosphorylation in the Ebola virus replication cycle. J Infect Dis. 2011;204(Suppl 3):S934–40.
149. Marzi A, et al. Vaccines. An Ebola whole-virus vaccine is protective in nonhuman primates. Science. 2015;348(6233):439–42.
150. Zhang AP, et al. The ebolavirus VP24 interferon antagonist: know your enemy. Virulence. 2012;3(5):440–5.
151. Zhang AP, et al. The ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel, pyramidal fold. PLoS Pathog. 2012;8(2):e1002550.
152. Gao J, Yin L. Drug development for controlling Ebola epidemic—a race against time. Drug Discov Ther. 2014;8(5):229–31.
153. Kudoyarova-Zubavichene NM, et al. Preparation and use of hyperimmune serum for prophylaxis and therapy of Ebola virus infections. J Infect Dis. 1999;179(Suppl 1):S218–23.
154. Jahrling PB, et al. State-of-the-art workshops on medical countermeasures potentially available for human use following accidental exposures to Ebola virus. J Infect Dis. 2015. doi:10.1093/infdis/jiv115
155. Pettitt J, et al. Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail. Sci Transl Med. 2013;5(199):199ra113.
156. Murin CD, et al. Structures of protective antibodies reveal sites of vulnerability on Ebola virus. Proc Natl Acad Sci USA. 2014;111(48):17182–7.
157. Kibuuka H, et al. Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial. Lancet. 2015;385(9977):1545–54.
158. Sarwar UN, et al. Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial. J Infect Dis. 2015;211(4):549–57.