THE USE OF MONOCLONAL ANTIBODIES FOR THE TREATMENT OF EBOLA VIRUS DISEASE

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Abstract

Some drugs candidates for treatment of Ebola virus disease (EVD), have been studied, monoclonal antibody (mAb) cocktails have shown great potential as EVD therapeutics. The advantages of mAb therapy include low toxicity, high specificity and versatility, with the range of biological effects being dependent upon the Fc region. Functions of mAbs include pathogen opsonisation, complement activation, antibody-dependent cell cytotoxicity and virus neutralization characteristics. The most known mAb cocktail, used as therapeutic, is ZMapр, manufactured by «Leaf Biopharmaceutical» from 2004. The elaborated mAb cocktails, structures and properties s of mAbs, the protective characteristics of mAbs and development of new pan-ebolavirus mAbs are reviewed in this article.

About the authors

T. E. Sizikova

48 Central Scientific Research Institute

Author for correspondence.
Email: noemail@neicon.ru
Russian Federation

G. V. Borisevich

48 Central Scientific Research Institute

Email: 48cnii@mil.ru
Russian Federation

D. V. Shcheblyakov

National Research Centre of Epidemiology and Microbiology named after honorary academician N.F. Gamaleya

Email: noemail@neicon.ru
Russian Federation

D. A. Burmistrova

National Research Centre of Epidemiology and Microbiology named after honorary academician N.F. Gamaleya

Email: noemail@neicon.ru
Russian Federation

V. N. Lebedev

48 Central Scientific Research Institute

Email: noemail@neicon.ru
Russian Federation

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  46. Geisbert T.W., Lee A.C.H., Robbins M., Geisbert J.B., Honko A.N., Sood V., 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. doi: 10.1016/S0140-6736(10)60357-1
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  51. Pettitt J., Zeitlin L., Kim do H., Working C., Johnson J.C., Bohorov O., et al. Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail. Sci. Transl. Med. 2013; 5(199): 1-6. doi: 10.1126/scitranslmed.3006608
  52. Olinger G.G., Pettitt J., Kim D., Working C., Bohorov O., Bratcher B., 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. doi: 10.1073/pnas.1213709109
  53. Davidson E., Bryan C., Fong R.H., Barnes T., Pfaff J.M., Mabila M., et al. Mechanism of Binding to Ebola Virus Glycoprotein by the ZMapp, ZMAb, and MB-003 Cocktail Antibodies. J. Virol. 2015; 89 (21): 10982-92. doi: 10.1128/jvi.01490-15
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  55. Wilson J.A., Hewey M., Bakken R., Guest S., Bray M., Schmaljohn A.L., et al. Epitopes involved in antibody-mediated protection from Ebola virus. Science. 2000; 287(5458): 1664-6.
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  57. Jones J.D. Leishmania tarentolae: an alternative approach to the production of monoclonal antibodies to treat emerging viral infections. Infect. Dis. Poverty. 2015; 4(8): 1-5. doi: 10.1186/2049-9957-4-8
  58. Zhang Y., Li D., Jin X., Huang Z. Fighting Ebola with ZMapp: spotlight on plant-made antibody. Sci. China Life Sci. 2014; 57(10): 987-8. doi: 10.1007/s11427-014-4746-7
  59. Furuyama W., Marzi A., Nanbo A., Haddock E., Maruyama J., Miyamoto H., et al. Discovery of an antibody for pan-ebolavirus therapy. Sci. Rep. 2016; 6(20514): 1-10. doi: 10.1038/srep20514
  60. Holtsberg F.W., Shulenin S., Vu H., Howell K.A., Patel S.J., Gunn B., et al. Pan-ebolavirus and Pan-filovirus Mouse Monoclonal Antibodies: Protection against Ebola and Sudan Viruses. J. Virol. 2015; 90(1): 266-78. doi: 10.1128/jvi.02171-15
  61. McCarthy M. US signs contract with ZMapp maker to accelerate development of the Ebola drug. BMJ. 2014; 349: 5488. doi: 10.1136/bmj.g5488
  62. WHO. Ebola situation report - 8 July 2015. Available at: http://apps.who.int/iris/bitstream/handle/10665/179196/roadmapsitrep_8Jul2015_eng.pdf
  63. Goodman J.L. Studing “secret serums”-toward safe, effective Ebola treatments. N. Engl. J. Med. 2014; 371(12):1086-9. doi: 10.1056/nejmp1409817
  64. Lyon G.M., Mehta A.K., Varkey J.B., Brantly K., Plyler L., McElroy A.K., et al. Clinical Care of Two Patients with Ebola Virus Disease in the United States. N. Engl. J. Med. 2014; 371(25): 2402-9. doi: 10.1056/nejmoa1409838

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