ИСПОЛЬЗОВАНИЕ МОНОКЛОНАЛЬНЫХ АНТИТЕЛ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ, ВЫЗВАННОГО ВИРУСОМ ЭБОЛА

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Вопросы вирусологии. 2018; 63: 245-249

ИСПОЛЬЗОВАНИЕ МОНОКЛОНАЛЬНЫХ АНТИТЕЛ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ, ВЫЗВАННОГО ВИРУСОМ ЭБОЛА

Сизикова Т. Е., Борисевич Г. В., Щебляков Д. В., Бурмистрова Д. А., Лебедев В. Н.

https://doi.org/10.18821/0507-4088-2018-63-6-245-249

Аннотация

Изучен ряд препаратов, рассматриваемых в качестве кандидатов для лечения заболевания, вызванного вирусом Эбола, из них наибольшим терапевтическим потенциалом обладают смеси моноклональных антител (МКАт). Преимущества использования МКАт заключаются в низкой токсичности, высокой специфичности и универсальности. Диапазон биологического действия МКАт зависит от Fc-фрагмента антител. Свойства МКАт включают опсонизацию патогена, активацию комплемента, антителозависимую клеточную цитотоксичность и вируснейтрализующие характеристики. Наиболее известной смесью МКАт, используемой для лечения, является ZMapр, производимая фирмой «Leaf Biopharmaceutical» с 2004 г. В статье рассмотрены разработанные смеси МКАт, их структура и свойства, защитная эффективность и создание новых видов МКАт, специфичных для всех представителей рода Еbolavirus.

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28. 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

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33. Feldmann H., Geisbert T.W. Ebola haemorrhagic fever. Lancet. 2011; 377(9768): 849-62. DOI: 10.1016/S0140-6736(10)60667-8

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35. Albarino C.G., Shoemaker T., Khristova M.L., Wamala J.F., Muyembe J.J., Balinandi S., et al. Genomic analysis of filoviruses associated with four viral hemorrhagic fever outbreaks in Uganda and the Democratic Republic of the Congo in 2012. Virology. 2013; 442(2): 97-100. DOI: 10.1016/j.virol.2013.04.014

36. Volchkov V.E., Feldmann H., Volchkova V.A., Klenk H.D. Processing of Ebola virus glycoprotein be polyprotein convertase furin. Proc. Nate Acad. Sci. USA Microbiology. 1998; 95(10): 5762-7.

37. Lee J.E., Fusco M.L., Hessell A.J., Oswald W.B., Burton D.R., Saphire E.O. Structure of Ebola virus glycoprotein bound to an antibody from a human survivor. Nature. 2008; 454(7201): 177-82. DOI: 10.1038/nature07082.

38. Lee J.E., Saphire E.O. Ebolavirus glycoprotein structure and mechanism of entry. Future Virol. 2009; 4(6): 621-35. DOI: 10.1038/nature07082

39. Wool-Lewis R.J., Bates P. Characterization of Ebola virus entry by using pseudotyped viruses: identification of receptor-deficient cell lines. J. Virol. 1998; 72(4): 3155-60.

40. Warfield K.L., Swenson D.L., Olinger G.G., Olinger G.G., Nichols D.K., Pratt W.D., et al. Gene-specific countermeasures against Ebola virus based on antisense phosphorodiamidate morpholino oligomers. PLoS Pathog. 2006; 2(1): 5-13. DOI: 10.1371/journal.ppat.0020001

41. Geisbert T.W., Geisbert T.W., Hensley L.E., Jahrling P.B., Larsen T., Geisbert J.B., 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. DOI:10.1016/s0140-6736(03)15012-x

42. Hensley L.E., Stewens E.L., Yan S.B., Geisbert J.B., Macias W.L., Larsen T., et al. Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever. J. Infect. Dis. 2007; 196(2): 390-9. DOI: 10.1086/520598

43. Madelain V., Nguyen T.H., Olivo A., de Lamballerie X., Guedj J., Taburet A.M., et al. Ebola Virus Infection: Review of the Pharmacokinetic and Pharmacodynamic Properties of Drugs Considered for Testing in Human Efficacy Trials. Clin. Pharmacokinet. 2016; 55(8): 907-23. DOI: 10.1007/s40262-015-0364-1

44. Olszanecki R., Gawlik G. Pharmacotherapy of Ebola hemorrhagic fever: a brief review of current status and future perspectives. Folia Med. Cracov. 2014; 54(3): 67-77.

45. Sayburn A. WHO gives go ahead for experimental treatments to be used in Ebola outbreak. BMJ. 2014; 349: 1. DOI: 10.1136/bmj.g5161

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

47. Qiu X., Wong G., Audet J., Bello A., Fernando L., Alimonti J.B., et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014; 514(7520): 47-53. DOI: 10.1038/nature13777

48. Choi W.Y., Hong K.J., Hong J.E., Lee W.J. Progress of vaccine and drug development for Ebola preparedness. Clin. Exp. Vaccine Res. 2015; 4(1): 11-6. DOI: 10.7774/cevr.2015.4.1.11

49. Murin C.D., Fusco M.L., Bornholdt Z.A., Qiu X., Olinger G.G., Zeitlin L., et al. Structures of protective antibodies reveal sites of vulnerability on Ebola virus. Proc Natl. Acad. Sci. USA. 2014; 111(48): 17182-7. DOI: 10.1073/pnas.1414164111

50. Na W., Park N., Yeom M., Song D. Ebola outbreak in Western Africa 2014: what is going on with Ebola virus? Clin. Exp. Vaccine Res. 2015; 4(1): 17-22. DOI: 10.7774/cevr.2015.4.1.17

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

54. Kugelman J.R., Kugelman-Tonos J., Ladner J.T., Pettit J., Keeton C.M., Nagle E.R., et al. Emergence of Ebola Virus Escape Variants in Infected Nonhuman Primates Treated with the MB-003 Antibody Cocktail. Cell. Rep. 2015; 12(12): 2111-20. DOI: 10.1016/j.celrep.2015.08.038

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.

56. Yang Z.Y., Duckers H.J., Sullivan N.J., Sanchez A., Nabel E.G., Nabel G.J. Identification of the Ebola virus glycoprotein as main viral determinant of vascular cell cytotoxicity and injury. Nat. Med. 2000; 6(8): 886-9. DOI: 10.1038/78645

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

Problems of Virology. 2018; 63: 245-249

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

Sizikova T. E., Borisevich G. V., Shcheblyakov D. V., Burmistrova D. A., Lebedev V. N.

https://doi.org/10.18821/0507-4088-2018-63-6-245-249

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.

References