mesЭкстремальная биомедицинаExtreme Medicine3033-89643033-8972Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2022.049mes-199Research ArticleОБЗОРREVIEWТехнологии создания вируснейтрализующих антител человека на примере SARS-CoV-2Neutralizing antibody creation technologies: case of SARS-CoV-2БаклаушевВ. П.BaklaushevV. P.

Владимир Павлович Баклаушев

Ореховый бульвар, д. 28, г. Москва, 115682

Vladimir P. Baklaushev

Orexovyj bul'var, 28, g. Moscow, 115682

baklaushev.vp@fnkc-fmba.ruСамойловаЕ. М.SamoilovaE. M.

Москва

Moscow

КузнецоваС. М.KuznetsovaS. M.

Москва

Moscow

ЕрмолаеваЕ. В.ErmolaevaE. V.

Москва

Moscow

ЮсубалиеваГ. М.YusubalievaG. M.

Москва

Moscow

КальсинВ. А.KalsinV. A.

Москва

Moscow

ЛипатоваА. В.LipatovaA. V.

Москва

Moscow

ТроицкийА. В.TroitskyA. V.

Москва

Moscow

Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий Федерального медико-биологического агентства; Институт молекулярной биологии имени В. А. Энгельгардта Российской академии наук; Научно-исследовательский институт пульмонологии Федерального медико-биологического агентстваРоссияFederal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies, Federal Medical Biological Agency of Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences; Research Institute of Pulmonology, Federal Medical Biological Agency of RussiaRussian FederationФедеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий Федерального медико-биологического агентства; Институт молекулярной биологии имени В. А. Энгельгардта Российской академии наукРоссияFederal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies, Federal Medical Biological Agency of Russia; Engelhardt Institute of Molecular Biology, Russian Academy of SciencesRussian FederationФедеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий Федерального медико-биологического агентстваРоссияFederal Scientific and Clinical Center of Specialized Types of Medical Care and Medical Technologies, Federal Medical Biological Agency of RussiaRussian FederationИнститут молекулярной биологии имени В. А. Энгельгардта Российской академии наукРоссияEngelhardt Institute of Molecular Biology, Russian Academy of SciencesRussian Federation202228102024244513Copyright © Баклаушев В.П., Самойлова Е.М., Кузнецова С.М., Ермолаева Е.В., Юсубалиева Г.М., Кальсин В.А., Липатова А.В., Троицкий А.В., 20242024Баклаушев В.П., Самойлова Е.М., Кузнецова С.М., Ермолаева Е.В., Юсубалиева Г.М., Кальсин В.А., Липатова А.В., Троицкий А.В.Baklaushev V.P., Samoilova E.M., Kuznetsova S.M., Ermolaeva E.V., Yusubalieva G.M., Kalsin V.A., Lipatova A.V., Troitsky A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/199

Моноклональные антитела (мАт) — самый перспективный и наиболее интенсивно пополняемый вид биоактивных фармпрепаратов. В настоящее время более 100 различных мАт одобрены FDA и другими регуляторами для терапии онкологических, инфекционных, системных, аутоиммунных и других заболеваний. Отдельным современным направлением является получение вируснейтрализующих антител к возбудителям социально значимых инфекций, таких как ВИЧ, вирусы гепатита, SARS-CoV-2. Пандемия новой коронавирусной инфекции показала, насколько актуально может быть наличие технологической платформы по производству полностью гуманизированных антител человека. Развитие технологии рекомбинантных ДНК и разработка фагового дисплея антител позволили создавать библиотеки антигенсвязывающих фрагментов и проводить скрининг с целевыми антигенами. В обзоре обсуждаются достоинства и недостатки фагового дисплея, в том числе с применением технологии однодоменных антител на основе вариабельного домена тяжелой цепи. Представлены описание и практические результаты наиболее современной технологии получения антител человека путем сортировки и секвенирования генома отдельных В-клеток памяти на примере получения моноклональных вируснейтрализующих антител против SARS-CoV-2. Описаны перспективы дальнейшего развития технологии получения рекомбинантных антител человека, в частности — создание последовательностей вариабельных фрагментов антител с помощью искусственного интеллекта.

Monoclonal antibodies (mAbs) are the most promising and most intensively replenished type of bioactive pharmaceuticals. Currently, there are over 100 different mAbs approved by the FDA and other regulating agencies for treatment of oncological, infectious, systemic, autoimmune and other diseases. Design of antibodies neutralizing pathogens of socially significant infections, such as HIV, hepatitis viruses, SARS-CoV-2, is a separate direction. The SARS-CoV-2 pandemic has shown how urgent it is to have a technological platform enabling production of fully human antibodies. The development of recombinant DNA technology and antibody phage display enabled compilation of libraries of antigen-binding fragments and screening with target antigens. This review discusses the advantages and disadvantages of phage display, including use of single-domain antibody technology based on the heavy chain variable domain. We describe the state-of-the-art (and practical results of its application) technology enabling production of human antibodies by sorting and sequencing the genome of individual memory B cells, using monoclonal virus-neutralizing antibodies against SARS-CoV-2 as an example. The prospects of further development of the recombinant human antibody production technology are discussed; in particular, we consider creation of sequences of variable fragments of antibodies with the help of artificial intelligence.

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