aidsВИЧ-инфекция и иммуносупрессииHIV Infection and Immunosuppressive Disorders2077-9828Baltic Medical Education Center10.22328/2077-9828-2021-13-3-aids-593Research ArticleАНАЛИТИЧЕСКИЙ ОБЗОРШироко нейтрализующие антитела для лечения ВИЧ-инфекцииBroadly neutralizing antibodies for the treatment of HIV infectionГлазковаДина ВикторовнаGlazkovaDina V

кандидат биологических наук, старший научный сотрудник

georgin2702@gmail.comБогословскаяЕлена ВладимировнаBogoslovskayaElena V

доктор медицинских наук, заведующий лабораторией разработки методов генной терапии

lenabo2@mail.ruШипулинГерман АлександровичShipulinGerman A

кандидат медицинских наук, заместитель директора по научно-производственной деятельности

shipgerman@gmail.comЮдинСергей МихайловичYudinSergei M

доктор медицинских наук, профессор, генеральный директор ФГБУ ЦСП ФМБА России

yudin@cspmz.ruФГБУ "ЦСП" ФМБА РоссииРоссияFederal State Budgetary Institution «Centre for Strategic Planning and Management of Biomedical Health Risks» of the Federal Medical Biological AgencyRussian Federation202106112021133593Copyright © Глазкова Д.В., Богословская Е.В., Шипулин Г.А., Юдин С.М., 20212021Глазкова Д.В., Богословская Е.В., Шипулин Г.А., Юдин С.М.Glazkova D.V., Bogoslovskaya E.V., Shipulin G.A., Yudin S.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://hiv.bmoc-spb.ru/jour/article/view/593

Антитела, обладающие нейтрализующей активностью в отношении широкого спектра субтипов вируса иммунодефицита человека 1 (обозначаемые термином broadly neutralizing antibodies (bnAbs)), представляют огромный интерес в качестве терапевтического агента для лечения ВИЧ-инфекции, поскольку при пассивной иммунизации они способны обеспечить защиту от большинства штаммов ВИЧ-1. В представленном обзоре обсуждаются механизмы формирования таких антител, их классификация по связыванию с консервативными областями оболочечного белка Env, а также присущие им особенности. Приведены данные по характеристикам наиболее перспективных для терапии bnAbs, а также их комбинаций. В последнем разделе подробно рассмотрены результаты проведенных на сегодняшний день клинических испытаний.

Antibodies with neutralizing activity against a wide range of human immunodeficiency virus 1 subtypes (known as broadly neutralizing antibodies (bNAb)) are of great interest as a therapeutic agent for the treatment of HIV infection, because they are able to provide natural protection against most HIV-1 strains. The review discusses the mechanisms of formation of bNAbs, their classification by binding to conservative regions of the envelope protein, as well as their intrinsic features. Description of the most promising bNAbs and their combinations is presented. In the last section the results of clinical trials available to date are reviewed in detail.

ВИЧшироко нейтрализующие антителаклинические испытанияHIVbroadly neutralizing antibodies (bnAbs)clinical trialsReferencesWang Q. and Zhang L. Broadly neutralizing antibodies and vaccine design against HIV-1 infection. // Front Med. 2020 Feb;14(1):30-42. doi: 10.1007/s11684-019-0721-9.Wang Q. and Zhang L. Broadly neutralizing antibodies and vaccine design against HIV-1 infection. // Front Med. 2020 Feb;14(1):30-42. doi: 10.1007/s11684-019-0721-9.Zhu P., Liu J., Bess J., Chertova E., Lifson J.D. et al. Distribution and three-dimensional structure of AIDS virus envelope spikes. // Nature. 2006 Jun 15;441(7095):847-52. doi: 10.1038/nature04817.Zhu P., Liu J., Bess J., Chertova E., Lifson J.D. et al. Distribution and three-dimensional structure of AIDS virus envelope spikes. // Nature. 2006 Jun 15;441(7095):847-52. doi: 10.1038/nature04817.Wyatt R. and Sodroski J. The HIV-1 Envelope Glycoproteins: Fusogens, Antigens, and Immunogens. // Science. 1998 Jun 19;280(5371):1884-8. doi: 10.1126/science.280.5371.1884Wyatt R. and Sodroski J. The HIV-1 Envelope Glycoproteins: Fusogens, Antigens, and Immunogens. // Science. 1998 Jun 19;280(5371):1884-8. doi: 10.1126/science.280.5371.1884Stewart-Jones G.B.E., Soto C., Lemmin T., Chuang G.Y. et al. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. // Cell. 2016 May 5;165(4):813-26. doi: 10.1016/j.cell.2016.04.010.Stewart-Jones G.B.E., Soto C., Lemmin T., Chuang G.Y. et al. Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. // Cell. 2016 May 5;165(4):813-26. doi: 10.1016/j.cell.2016.04.010.Walker L.M., Phogat S.K., Chan-Hui Po-Y., Wagner D. et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. // Science. 2009 Oct 9;326(5950):285-9. doi: 10.1126/science.1178746.Walker L.M., Phogat S.K., Chan-Hui Po-Y., Wagner D. et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. // Science. 2009 Oct 9;326(5950):285-9. doi: 10.1126/science.1178746.Alam S.M., McAdams M., Boren D., Rak M. et al. The Role of Antibody Polyspecificity and Lipid Reactivity in Binding of Broadly Neutralizing Anti-HIV-1 Envelope Human Monoclonal Antibodies 2F5 and 4E10 to Glycoprotein 41 Membrane Proximal Envelope Epitopes. // J. Immunol. 2007 Apr 1;178(7):4424-35. doi: 10.4049/jimmunol.178.7.4424.Alam S.M., McAdams M., Boren D., Rak M. et al. The Role of Antibody Polyspecificity and Lipid Reactivity in Binding of Broadly Neutralizing Anti-HIV-1 Envelope Human Monoclonal Antibodies 2F5 and 4E10 to Glycoprotein 41 Membrane Proximal Envelope Epitopes. // J. Immunol. 2007 Apr 1;178(7):4424-35. doi: 10.4049/jimmunol.178.7.4424.Liao H.-X., Chen Xi, Munshaw S., Zhang R. et al. Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated. // J. Exp. Med. 2011 Oct 24;208(11):2237-49. doi: 10.1084/jem.20110363.Liao H.-X., Chen Xi, Munshaw S., Zhang R. et al. Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated. // J. Exp. Med. 2011 Oct 24;208(11):2237-49. doi: 10.1084/jem.20110363.Haynes B.F., Fleming J., Clair E.W.St. et al. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. // Science. 2005 Jun 24;308(5730):1906-8. doi: 10.1126/science.1111781.Haynes B.F., Fleming J., Clair E.W.St. et al. Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies. // Science. 2005 Jun 24;308(5730):1906-8. doi: 10.1126/science.1111781.Matyas G.R., Beck Z., Karasavvas N., Alving C.R. Lipid binding properties of 4E10, 2F5, and WR304 monoclonal antibodies that neutralize HIV-1. // Biochim Biophys Acta. 2009 Mar;1788(3):660-5. doi: 10.1016/j.bbamem.2008.11.015.Matyas G.R., Beck Z., Karasavvas N., Alving C.R. Lipid binding properties of 4E10, 2F5, and WR304 monoclonal antibodies that neutralize HIV-1. // Biochim Biophys Acta. 2009 Mar;1788(3):660-5. doi: 10.1016/j.bbamem.2008.11.015.Barbas C.F. III, Björling E., Chiodi F., Dunlop N., Cababa D. et al. Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro. // Proc. Natl. Acad. Sci. USA. 1992 Oct 1;89(19):9339-43. doi: 10.1073/pnas.89.19.9339.Barbas C.F. III, Björling E., Chiodi F., Dunlop N., Cababa D. et al. Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro. // Proc. Natl. Acad. Sci. USA. 1992 Oct 1;89(19):9339-43. doi: 10.1073/pnas.89.19.9339.Burton D., Pyati J., Koduri R., Sharp S.J. et al. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. // Science. 1994 Nov 11;266(5187):1024-7. doi: 10.1126/science.7973652.Burton D., Pyati J., Koduri R., Sharp S.J. et al. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. // Science. 1994 Nov 11;266(5187):1024-7. doi: 10.1126/science.7973652.Gorny M.K., Conley A.J., Karwowska S., Buchbinder A., Xu J.Y., Emini E.A., Koenig S., Zolla-Pazner S. Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody. // J. Virol. 1992 Vol. 66 (12). P. 7538-42. doi: 10.1128/JVI.66.12.7538-7542.1992.Gorny M.K., Conley A.J., Karwowska S., Buchbinder A., Xu J.Y., Emini E.A., Koenig S., Zolla-Pazner S. Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody. // J. Virol. 1992 Vol. 66 (12). P. 7538-42. doi: 10.1128/JVI.66.12.7538-7542.1992.Muster T., Steindl F., Purtscher M., Trkola A., Klima A., Himmler G., Rüker F., Katinger H. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. // J. Virol. 1993 Nov;67(11):6642-7. doi: 10.1128/JVI.67.11.6642-6647.1993.Muster T., Steindl F., Purtscher M., Trkola A., Klima A., Himmler G., Rüker F., Katinger H. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. // J. Virol. 1993 Nov;67(11):6642-7. doi: 10.1128/JVI.67.11.6642-6647.1993.Stiegler G., Kunert R., Purtscher M., Wolbank S., Voglauer R., Steindl F., Katinger H. A Potent Cross-Clade Neutralizing Human Monoclonal Antibody against a Novel Epitope on gp41 of Human Immunodeficiency Virus Type 1. // AIDS Res. Hum. Retroviruses. 2001 Dec 10;17(18):1757-65. doi: 10.1089/08892220152741450.Stiegler G., Kunert R., Purtscher M., Wolbank S., Voglauer R., Steindl F., Katinger H. A Potent Cross-Clade Neutralizing Human Monoclonal Antibody against a Novel Epitope on gp41 of Human Immunodeficiency Virus Type 1. // AIDS Res. Hum. Retroviruses. 2001 Dec 10;17(18):1757-65. doi: 10.1089/08892220152741450.Zwick M.B., Labrijn A.F., Wang M., Spenlehaueret C. et al. Broadly Neutralizing Antibodies Targeted to the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 Glycoprotein gp41. // J. Virol. 2001 Nov;75(22):10892-905. doi: 10.1128/JVI.75.22.10892-10905.2001.Zwick M.B., Labrijn A.F., Wang M., Spenlehaueret C. et al. Broadly Neutralizing Antibodies Targeted to the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 Glycoprotein gp41. // J. Virol. 2001 Nov;75(22):10892-905. doi: 10.1128/JVI.75.22.10892-10905.2001.Wei X., Decker J.M., Wang S., Hui H. et al. Antibody neutralization and escape by HIV-1. // Nature. 2003 Mar 20;422(6929):307-12. doi: 10.1038/nature01470.Wei X., Decker J.M., Wang S., Hui H. et al. Antibody neutralization and escape by HIV-1. // Nature. 2003 Mar 20;422(6929):307-12. doi: 10.1038/nature01470.Richman D.D., Wrin T., Little S.J., Petropoulos C.J. et al. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. // Proc. Natl. Acad. Sci. U. S. A. 2003 Apr 1;100(7):4144-9. doi: 10.1073/pnas.0630530100.Richman D.D., Wrin T., Little S.J., Petropoulos C.J. et al. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. // Proc. Natl. Acad. Sci. U. S. A. 2003 Apr 1;100(7):4144-9. doi: 10.1073/pnas.0630530100.Mascola J.R. and Haynes B.F. HIV-1 neutralizing antibodies: understanding nature’s pathways. // Immunol. Rev. 2013 Jul;254(1):225-44. doi: 10.1111/imr.12075.Mascola J.R. and Haynes B.F. HIV-1 neutralizing antibodies: understanding nature’s pathways. // Immunol. Rev. 2013 Jul;254(1):225-44. doi: 10.1111/imr.12075.Rusert P., Kouyos R.D., Kadelka C., Ebner H. et al. Determinants of HIV-1 broadly neutralizing antibody induction. // Nat. Med. 2016 Nov;22(11):1260-1267. doi: 10.1038/nm.4187.Rusert P., Kouyos R.D., Kadelka C., Ebner H. et al. Determinants of HIV-1 broadly neutralizing antibody induction. // Nat. Med. 2016 Nov;22(11):1260-1267. doi: 10.1038/nm.4187.Subbaraman H., Schanz M., Trkola A. Broadly neutralizing antibodies: What is needed to move from a rare event in HIV-1 infection to vaccine efficacy? // Retrovirology. 2018 Jul 28;15(1):52. doi: 10.1186/s12977-018-0433-2.Subbaraman H., Schanz M., Trkola A. Broadly neutralizing antibodies: What is needed to move from a rare event in HIV-1 infection to vaccine efficacy? // Retrovirology. 2018 Jul 28;15(1):52. doi: 10.1186/s12977-018-0433-2.Dugast A.-S., Arnold K., Lofano G., Moore S. et al. Virus-driven Inflammation Is Associated with the Development of bNAbs in Spontaneous Controllers of HIV. // Clin. Infect. Dis. 2017 Apr 15;64(8):1098-1104. doi: 10.1093/cid/cix057.Dugast A.-S., Arnold K., Lofano G., Moore S. et al. Virus-driven Inflammation Is Associated with the Development of bNAbs in Spontaneous Controllers of HIV. // Clin. Infect. Dis. 2017 Apr 15;64(8):1098-1104. doi: 10.1093/cid/cix057.Aasa-Chapman M.M., Hayman A., Newton P., Cornforth D. et al. Development of the antibody response in acute HIV-1 infection. // AIDS. 2004 Feb 20;18(3):371-81. doi: 10.1097/00002030-200402200-00002.Aasa-Chapman M.M., Hayman A., Newton P., Cornforth D. et al. Development of the antibody response in acute HIV-1 infection. // AIDS. 2004 Feb 20;18(3):371-81. doi: 10.1097/00002030-200402200-00002.Mikell I., Sather D.N., Kalams S.A., Altfeld M., Alter G., Stamatatos L. et al. Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1. // PLoS Pathog. 2011 Jan 13;7(1):e1001251. doi: 10.1371/journal.ppat.1001251.Mikell I., Sather D.N., Kalams S.A., Altfeld M., Alter G., Stamatatos L. et al. Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1. // PLoS Pathog. 2011 Jan 13;7(1):e1001251. doi: 10.1371/journal.ppat.1001251.Landais E. and Moore P.L. Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers. // Retrovirology. 2018 Sep 5;15(1):61. doi: 10.1186/s12977-018-0443-0.Landais E. and Moore P.L. Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers. // Retrovirology. 2018 Sep 5;15(1):61. doi: 10.1186/s12977-018-0443-0.Doria-Rose N.A., Schramm C.A., Gorman J., Moore P.L. et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. // Nature. 2014 May 1;509(7498):55-62. doi: 10.1038/nature13036.Doria-Rose N.A., Schramm C.A., Gorman J., Moore P.L. et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. // Nature. 2014 May 1;509(7498):55-62. doi: 10.1038/nature13036.Klein F., Diskin R., Scheid J.F., Gaebler C. et al. Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. // Cell. 2013 Mar 28;153(1):126-38. doi: 10.1016/j.cell.2013.03.018.Klein F., Diskin R., Scheid J.F., Gaebler C. et al. Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. // Cell. 2013 Mar 28;153(1):126-38. doi: 10.1016/j.cell.2013.03.018.Kepler T.B., Liao H.-X., Alam SM., Bhaskarabhatla R. et al. Immunoglobulin Gene Insertions and Deletions in the Affinity Maturation of HIV-1 Broadly Reactive Neutralizing Antibodies. // Cell Host Microbe. 2014 Sep 10;16(3):304-13. doi: 10.1016/j.chom.2014.08.006.Kepler T.B., Liao H.-X., Alam SM., Bhaskarabhatla R. et al. Immunoglobulin Gene Insertions and Deletions in the Affinity Maturation of HIV-1 Broadly Reactive Neutralizing Antibodies. // Cell Host Microbe. 2014 Sep 10;16(3):304-13. doi: 10.1016/j.chom.2014.08.006.Wardemann H., Yurasov S., Schaefer A., Young J.W., Meffre E., Nussenzweig M.C. Predominant Autoantibody Production by Early Human B Cell Precursors. // Science. 2003 Sep 5;301(5638):1374-7. doi: 10.1126/science.1086907.Wardemann H., Yurasov S., Schaefer A., Young J.W., Meffre E., Nussenzweig M.C. Predominant Autoantibody Production by Early Human B Cell Precursors. // Science. 2003 Sep 5;301(5638):1374-7. doi: 10.1126/science.1086907.Mouquet H., Scheid J.F., Zoller M.J., Krogsgaard M. et al. Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation. // Nature. 2010 Sep 30;467(7315):591-5. doi: 10.1038/nature09385.Mouquet H., Scheid J.F., Zoller M.J., Krogsgaard M. et al. Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation. // Nature. 2010 Sep 30;467(7315):591-5. doi: 10.1038/nature09385.Diskin R., Scheid J.F., Marcovecchio P.M. et al. Increasing the Potency and Breadth of an HIV Antibody by using Structure-Based Rational Design. // Science. 2011 Dec 2;334(6060):1289-93. doi: 10.1126/science.1213782.Diskin R., Scheid J.F., Marcovecchio P.M. et al. Increasing the Potency and Breadth of an HIV Antibody by using Structure-Based Rational Design. // Science. 2011 Dec 2;334(6060):1289-93. doi: 10.1126/science.1213782.Yang G., Holl TM., Liu Y., Li Y., Lu X. et al. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. // J. Exp. Med. 2013 Feb 11;210(2):241-56. doi: 10.1084/jem.20121977.Yang G., Holl TM., Liu Y., Li Y., Lu X. et al. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. // J. Exp. Med. 2013 Feb 11;210(2):241-56. doi: 10.1084/jem.20121977.Scheid J.F., Mouquet H., Ueberheide B., Diskin R. et al. Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. // Science. 2011 Sep 16;333(6049):1633-7. doi: 10.1126/science.1207227.Scheid J.F., Mouquet H., Ueberheide B., Diskin R. et al. Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding. // Science. 2011 Sep 16;333(6049):1633-7. doi: 10.1126/science.1207227.Zhou P., Wang H., Fang M., Li Y. et al. Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies. // PLOS Pathog. 2019 Jun 13;15(6). P. e1007819. doi: 10.1371/journal.ppat.1007819.Zhou P., Wang H., Fang M., Li Y. et al. Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies. // PLOS Pathog. 2019 Jun 13;15(6). P. e1007819. doi: 10.1371/journal.ppat.1007819.Asokan M., Rudicell R.S., Louder M., McKee K. et al. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. // J. Virol. 2015 Dec;89(24):12501-12. doi: 10.1128/JVI.02097-15.Asokan M., Rudicell R.S., Louder M., McKee K. et al. Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope Exhibit Broad and Potent Neutralization. // J. Virol. 2015 Dec;89(24):12501-12. doi: 10.1128/JVI.02097-15.Wagh K., Seaman M.S., Zingg M., Fitzsimons T. et al. Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections. // PLoS Pathog. 2018 Mar 5;14(3):e1006860. doi: 10.1371/journal.ppat.1006860.Wagh K., Seaman M.S., Zingg M., Fitzsimons T. et al. Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections. // PLoS Pathog. 2018 Mar 5;14(3):e1006860. doi: 10.1371/journal.ppat.1006860.Xu L., Pegu A., Rao E., Doria-Rose N. et al. Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. // Science. 2017 Oct 6;358(6359):85-90. doi: 10.1126/science.aan8630.Xu L., Pegu A., Rao E., Doria-Rose N. et al. Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. // Science. 2017 Oct 6;358(6359):85-90. doi: 10.1126/science.aan8630.Steinhardt J.J., Guenaga J., Turner H.L., McKee K. et al. Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity. // Nat. Commun. 2018 Feb 28;9(1):877. doi: 10.1038/s41467-018-03335-4.Steinhardt J.J., Guenaga J., Turner H.L., McKee K. et al. Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity. // Nat. Commun. 2018 Feb 28;9(1):877. doi: 10.1038/s41467-018-03335-4.Ko S.-Y., Pegu A., Rudicell R.S., Yang Z.-y. et al. Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. // Nature. 2014 Oct 30;514(7524):642-5. doi: 10.1038/nature13612.Ko S.-Y., Pegu A., Rudicell R.S., Yang Z.-y. et al. Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. // Nature. 2014 Oct 30;514(7524):642-5. doi: 10.1038/nature13612.Gaudinski M.R., Coates E.E., Houser K.V., Chen G.L. et al. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults. // PLoS Med. 2018 Jan 24;15(1):e1002493. doi: 10.1371/journal.pmed.1002493.Gaudinski M.R., Coates E.E., Houser K.V., Chen G.L. et al. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults. // PLoS Med. 2018 Jan 24;15(1):e1002493. doi: 10.1371/journal.pmed.1002493.Gautam R., Nishimura Y., Pegu A., Nason M.C. et al. A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges. // Nature 2016 May 5;533(7601):105-109. doi: 10.1038/nature17677.Gautam R., Nishimura Y., Pegu A., Nason M.C. et al. A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges. // Nature 2016 May 5;533(7601):105-109. doi: 10.1038/nature17677.Simek M.D., Rida W., Priddy F.H., Pung P. et al. Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm. // J. Virol. 2009 Jul;83(14):7337-48. doi: 10.1128/JVI.00110-09.Simek M.D., Rida W., Priddy F.H., Pung P. et al. Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm. // J. Virol. 2009 Jul;83(14):7337-48. doi: 10.1128/JVI.00110-09.Binley J.M., Wrin T., Korber B., Zwick M.B. et al. Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies. // J. Virol. 2004 Dec;78(23):13232-52. doi: 10.1128/JVI.78.23.13232-13252.2004.Binley J.M., Wrin T., Korber B., Zwick M.B. et al. Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies. // J. Virol. 2004 Dec;78(23):13232-52. doi: 10.1128/JVI.78.23.13232-13252.2004.Babcook J.S., Leslie K.B., Olsen O.A., Salmon R.A., Schrader J.W. A novel strategy for generating monoclonal antibodies from single, isolated lymphocytes producing antibodies of defined specificities. // Proc. Natl. Acad. Sci. 1996 Jul 23;93(15):7843-8. doi: 10.1073/pnas.93.15.7843.Babcook J.S., Leslie K.B., Olsen O.A., Salmon R.A., Schrader J.W. A novel strategy for generating monoclonal antibodies from single, isolated lymphocytes producing antibodies of defined specificities. // Proc. Natl. Acad. Sci. 1996 Jul 23;93(15):7843-8. doi: 10.1073/pnas.93.15.7843.Tiller T., Meffre E., Yurasov S., Tsuiji M., Nussenzweig M.C., Wardemann H. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. // J. Immunol. Methods. 2008 Jan 1;329(1-2):112-24. doi: 10.1016/j.jim.2007.09.017.Tiller T., Meffre E., Yurasov S., Tsuiji M., Nussenzweig M.C., Wardemann H. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. // J. Immunol. Methods. 2008 Jan 1;329(1-2):112-24. doi: 10.1016/j.jim.2007.09.017.West A.P., Scharf L., Scheid J.F., Klein F., Bjorkman P.J., Nussenzweig M.C. Structural Insights on the Role of Antibodies in HIV-1 Vaccine and Therapy. // Cell. 2014 Feb 13;156(4):633-48. doi: 10.1016/j.cell.2014.01.052.West A.P., Scharf L., Scheid J.F., Klein F., Bjorkman P.J., Nussenzweig M.C. Structural Insights on the Role of Antibodies in HIV-1 Vaccine and Therapy. // Cell. 2014 Feb 13;156(4):633-48. doi: 10.1016/j.cell.2014.01.052.Wu X., Yang Z.Y., Li Y., et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1 // Science. 2010. Vol. 329 (5993). P. 856-861. DOI: 10.1126/science.1187659Wu X., Yang Z.Y., Li Y., et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1 // Science. 2010. Vol. 329 (5993). P. 856-861. DOI: 10.1126/science.1187659Rudicell R.S., Kwon Y.D., Ko S.Y., et al. Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo // J Virol. 2014. Vol. 88 (21). P. 12669-12682. DOI: 10.1128/JVI.02213-14Rudicell R.S., Kwon Y.D., Ko S.Y., et al. Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo // J Virol. 2014. Vol. 88 (21). P. 12669-12682. DOI: 10.1128/JVI.02213-14Huang J., Kang B.H., Ishida E., et al. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth // Immunity. 2016. Vol. 45 (5). P. 1108-1121. DOI: 10.1016/j.immuni.2016.10.027Huang J., Kang B.H., Ishida E., et al. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth // Immunity. 2016. Vol. 45 (5). P. 1108-1121. DOI: 10.1016/j.immuni.2016.10.027Julg B., Pegu A , Abbink P , et al. Virological Control by the CD4-Binding Site Antibody N6 in Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys // J Virol. 2017. Vol. 91 (16). P. e00498-17. DOI: 10.1128/JVI.00498-17Julg B., Pegu A , Abbink P , et al. Virological Control by the CD4-Binding Site Antibody N6 in Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys // J Virol. 2017. Vol. 91 (16). P. e00498-17. DOI: 10.1128/JVI.00498-17Scheid J.F., Horwitz J.A., Bar-On Y., et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption // Nature. 2016. Vol. 535 (7613). P. 556-560. DOI: 10.1038/nature18929Scheid J.F., Horwitz J.A., Bar-On Y., et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption // Nature. 2016. Vol. 535 (7613). P. 556-560. DOI: 10.1038/nature18929Shingai M., Nishimura Y., Klein F., et al. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia // Nature. 2013. Vol. 503 (7475). P. 277-280. DOI: 10.1038/nature12746Shingai M., Nishimura Y., Klein F., et al. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia // Nature. 2013. Vol. 503 (7475). P. 277-280. DOI: 10.1038/nature12746Nishimura Y., Gautam R., Chun T.W., et al. Early antibody therapy can induce long-lasting immunity to SHIV // Nature. 2017. Vol. 543 (7646). P. 559-563. DOI: 10.1038/nature21435Nishimura Y., Gautam R., Chun T.W., et al. Early antibody therapy can induce long-lasting immunity to SHIV // Nature. 2017. Vol. 543 (7646). P. 559-563. DOI: 10.1038/nature21435Sajadi M.M., Dashti A., Rikhtegaran Tehrani Z., et al. Identification of Near-Pan-neutralizing Antibodies against HIV-1 by Deconvolution of Plasma Humoral Responses // Cell. 2018. Vol. 173 (7). P. 1783-1795. DOI: 10.1016/j.cell.2018.03.061Sajadi M.M., Dashti A., Rikhtegaran Tehrani Z., et al. Identification of Near-Pan-neutralizing Antibodies against HIV-1 by Deconvolution of Plasma Humoral Responses // Cell. 2018. Vol. 173 (7). P. 1783-1795. DOI: 10.1016/j.cell.2018.03.061Walker L.M., Huber M., Doores K.J., et al. Broad neutralization coverage of HIV by multiple highly potent antibodies // Nature. 2011. Vol. 477 (7365). P. 466-470. DOI: 10.1038/nature10373Walker L.M., Huber M., Doores K.J., et al. Broad neutralization coverage of HIV by multiple highly potent antibodies // Nature. 2011. Vol. 477 (7365). P. 466-470. DOI: 10.1038/nature10373Mouquet H., Scharf L., Euler Z., et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies // Proc Natl Acad Sci U S A. 2012. Vol. 109(47). P. E3268-E3277. DOI: 10.1073/pnas.1217207109Mouquet H., Scharf L., Euler Z., et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies // Proc Natl Acad Sci U S A. 2012. Vol. 109(47). P. E3268-E3277. DOI: 10.1073/pnas.1217207109Nishimura Y., Gautam R., Chun T.W., et al. Early antibody therapy can induce long-lasting immunity to SHIV // Nature. 2017. Vol. 543 (7646). P. 559-563. DOI: 10.1038/nature21435Nishimura Y., Gautam R., Chun T.W., et al. Early antibody therapy can induce long-lasting immunity to SHIV // Nature. 2017. Vol. 543 (7646). P. 559-563. DOI: 10.1038/nature21435Sanders R.W., Derking R., Cupo A., et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies // PLoS Pathog. 2013. Vol. 9 (9). P. e1003618. DOI: 10.1371/journal.ppat.1003618Sanders R.W., Derking R., Cupo A., et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies // PLoS Pathog. 2013. Vol. 9 (9). P. e1003618. DOI: 10.1371/journal.ppat.1003618Doria-Rose N.A., Bhiman J.N., Roark R.S., et al. New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency // J Virol. 2015. Vol. 90(1). P. 76-91. DOI: 10.1128/JVI.01791-15Doria-Rose N.A., Bhiman J.N., Roark R.S., et al. New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency // J Virol. 2015. Vol. 90(1). P. 76-91. DOI: 10.1128/JVI.01791-15Sok D., van Gils M.J., Pauthner M., et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex // Proc Natl Acad Sci U S A. 2014. Vol. 111 (49). P. 17624-17629. DOI: 10.1073/pnas.1415789111Sok D., van Gils M.J., Pauthner M., et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex // Proc Natl Acad Sci U S A. 2014. Vol. 111 (49). P. 17624-17629. DOI: 10.1073/pnas.1415789111Huang J., Ofek G., Laub L., et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody // Nature. 2012. Vol. 491 (7424). P. 406-412. DOI: 10.1038/nature11544Huang J., Ofek G., Laub L., et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody // Nature. 2012. Vol. 491 (7424). P. 406-412. DOI: 10.1038/nature11544Williams L.D., Ofek G., Schätzle S., et al. Potent and broad HIV-neutralizing antibodies in memory B cells and plasma // Sci Immunol. 2017. Vol. 2 (7). P. eaal2200. DOI: 10.1126/sciimmunol.aal2200Williams L.D., Ofek G., Schätzle S., et al. Potent and broad HIV-neutralizing antibodies in memory B cells and plasma // Sci Immunol. 2017. Vol. 2 (7). P. eaal2200. DOI: 10.1126/sciimmunol.aal2200Wagh K., Bhattacharya T., Williamson C., et al. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection // PLoS Pathog. 2016. Vol. 12 (3). P. e1005520. DOI: 10.1371/journal.ppat.1005520Wagh K., Bhattacharya T., Williamson C., et al. Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection // PLoS Pathog. 2016. Vol. 12 (3). P. e1005520. DOI: 10.1371/journal.ppat.1005520Julg B., Liu P.T., Wagh K., et al. Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail // Sci Transl Med. 2017. Vol. 9 (408). P. eaao4235. DOI: 10.1126/scitranslmed.aao4235Julg B., Liu P.T., Wagh K., et al. Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail // Sci Transl Med. 2017. Vol. 9 (408). P. eaao4235. DOI: 10.1126/scitranslmed.aao4235Pegu A., Hessell A.J., Mascola J.R., Haigwood N.L. Use of broadly neutralizing antibodies for HIV-1 prevention // Immunol Rev. 2017. Vol. 275 (1). P. 296-312. DOI: 10.1111/imr.12511Pegu A., Hessell A.J., Mascola J.R., Haigwood N.L. Use of broadly neutralizing antibodies for HIV-1 prevention // Immunol Rev. 2017. Vol. 275 (1). P. 296-312. DOI: 10.1111/imr.12511Cavacini L.A., Samore M.H., Gambertoglio J., et al. Phase I study of a human monoclonal antibody directed against the CD4-binding site of HIV type 1 glycoprotein 120 // AIDS Res Hum Retroviruses. 1998. Vol. 14 (7). P. 545-550. DOI: 10.1089/aid.1998.14.545Cavacini L.A., Samore M.H., Gambertoglio J., et al. Phase I study of a human monoclonal antibody directed against the CD4-binding site of HIV type 1 glycoprotein 120 // AIDS Res Hum Retroviruses. 1998. Vol. 14 (7). P. 545-550. DOI: 10.1089/aid.1998.14.545Caskey M., Klein F., Lorenzi J.C., et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117 // Nature. 2015. Vol. 522 (7557). P. 487-491. DOI: 10.1038/nature14411Caskey M., Klein F., Lorenzi J.C., et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117 // Nature. 2015. Vol. 522 (7557). P. 487-491. DOI: 10.1038/nature14411Ledgerwood J.E., Coates E.E., Yamshchikov G., et al. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults // Clin Exp Immunol. 2015. Vol. 182 (3). P. 289-301. DOI: 10.1111/cei.12692Ledgerwood J.E., Coates E.E., Yamshchikov G., et al. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults // Clin Exp Immunol. 2015. Vol. 182 (3). P. 289-301. DOI: 10.1111/cei.12692Caskey M., Schoofs T., Gruell H., et al. Antibody 10-1074 suppresses viremia in HIV-1-infected individuals // Nat Med. 2017. Vol. 23 (2). P. 185-191. DOI: 10.1038/nm.4268Caskey M., Schoofs T., Gruell H., et al. Antibody 10-1074 suppresses viremia in HIV-1-infected individuals // Nat Med. 2017. Vol. 23 (2). P. 185-191. DOI: 10.1038/nm.4268Lynch R.M., Boritz E., Coates E.E., et al. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection // Sci Transl Med. 2015. Vol. 7 (319). P. 319ra206. DOI: 10.1126/scitranslmed.aad5752Lynch R.M., Boritz E., Coates E.E., et al. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection // Sci Transl Med. 2015. Vol. 7 (319). P. 319ra206. DOI: 10.1126/scitranslmed.aad5752Bar K.J., Sneller M.C., Harrison L.J., et al. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption // N Engl J Med. 2016. Vol. 375 (21). P. 2037-2050. DOI: 10.1056/NEJMoa1608243Bar K.J., Sneller M.C., Harrison L.J., et al. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption // N Engl J Med. 2016. Vol. 375 (21). P. 2037-2050. DOI: 10.1056/NEJMoa1608243Mendoza P., Gruell H., Nogueira L., et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression // Nature. 2018. Vol. 561 (7724). P. 479-484. DOI: 10.1038/s41586-018-0531-2Mendoza P., Gruell H., Nogueira L., et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression // Nature. 2018. Vol. 561 (7724). P. 479-484. DOI: 10.1038/s41586-018-0531-2Niessl J., Baxter A.E., Mendoza P., et al. Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity // Nat Med. 2020. Vol. 26 (2). P. 222-227. DOI: 10.1038/s41591-019-0747-1Niessl J., Baxter A.E., Mendoza P., et al. Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity // Nat Med. 2020. Vol. 26 (2). P. 222-227. DOI: 10.1038/s41591-019-0747-1Bar-On Y, Gruell H, Schoofs T, et al. Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals // Nat Med. 2018. Vol. 24 (11). P. 1701-1707. DOI: 10.1038/s41591-018-0186-4Bar-On Y, Gruell H, Schoofs T, et al. Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals // Nat Med. 2018. Vol. 24 (11). P. 1701-1707. DOI: 10.1038/s41591-018-0186-4Mahomed S., Garrett N., Karim Q.A., et al. Assessing the safety and pharmacokinetics of the anti-HIV monoclonal antibody CAP256V2LS alone and in combination with VRC07-523LS and PGT121 in South African women: study protocol for the first-in-human CAPRISA 012B phase I clinical trial // BMJ Open. 2020. Vol. 10 (11). P. e042247. DOI: 10.1136/bmjopen-2020-042247Mahomed S., Garrett N., Karim Q.A., et al. Assessing the safety and pharmacokinetics of the anti-HIV monoclonal antibody CAP256V2LS alone and in combination with VRC07-523LS and PGT121 in South African women: study protocol for the first-in-human CAPRISA 012B phase I clinical trial // BMJ Open. 2020. Vol. 10 (11). P. e042247. DOI: 10.1136/bmjopen-2020-042247

The authors declare that there are no conflicts of interest present.