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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">biopreparat</journal-id><journal-title-group><journal-title xml:lang="ru">БИОпрепараты. Профилактика, диагностика, лечение</journal-title><trans-title-group xml:lang="en"><trans-title>Biological Products. Prevention, Diagnosis, Treatment</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2221-996X</issn><issn pub-type="epub">2619-1156</issn><publisher><publisher-name>Scientific Centre for Expert Evaluation of Medicinal Products</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.30895/2221-996X-2025-25-4-376-388</article-id><article-id custom-type="elpub" pub-id-type="custom">biopreparat-675</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ТЕМА НОМЕРА: ПРЕПАРАТЫ МОНОКЛОНАЛЬНЫХ АНТИТЕЛ И ИММУНОГЛОБУЛИНОВ: ОТ РАЗРАБОТКИ ДО КЛИНИЧЕСКОГО ПРИМЕНЕНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ISSUE TOPIC: MONOCLONAL ANTIBODIES AND IMMUNOGLOBULINS: FROM DESIGN TO CLINICAL USE</subject></subj-group></article-categories><title-group><article-title>Защитная эффективность комбинированного препарата моноклональных антител докаравимаба и миромавимаба в отношении классического вируса бешенства: доклиническое исследование на мышах BALB/с</article-title><trans-title-group xml:lang="en"><trans-title>Protective efficacy of combined monoclonal antibody docaravimab and miromavimab preparation against classical rabies virus: A preclinical study in BALB/c mice</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6742-3919</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Борисевич</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Borisevich</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Борисевич Сергей Владимирович, д-р биол. наук, проф., академик РАН </p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Sergey V. Borisevich, Dr. Sci. (Biol.), Prof., Acad. RAS</p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><email xlink:type="simple">48cnii@mil.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4387-0367</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рубцов</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Rubtsov</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Рубцов Владимир Васильевич, канд. вет. наук </p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Vladimir V. Rubtsov, Cand. Sci. (Vet.)</p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8183-9224</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Писцов</surname><given-names>М. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Pistsov</surname><given-names>M. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Писцов Михаил Николаевич, канд. биол. наук, ст. науч. сотр. </p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Mikhail N. Pistsov, Cand. Sci. (Biol.), Senior Res.</p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6732-8404</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Логинова</surname><given-names>С. Я.</given-names></name><name name-style="western" xml:lang="en"><surname>Loginova</surname><given-names>S. Ya.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Логинова Светлана Яковлевна, д-р биол. наук </p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Svetlana Ya. Loginova, Dr. Sci. (Biol.) </p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7674-2321</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кротков</surname><given-names>В. Т.</given-names></name><name name-style="western" xml:lang="en"><surname>Krotkov</surname><given-names>V. T.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кротков Виктор Тимофеевич, д-р биол. наук, ст. науч. сотр. </p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Viktor T. Krotkov, Dr. Sci. (Biol.), Senior Res.</p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6155-1365</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сахаров</surname><given-names>Р. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Sakharov</surname><given-names>R. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сахаров Роман Владимирович</p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Roman V. Sakharov</p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1647-5783</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кузнецов</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kuznetsov</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кузнецов Денис Анатольевич</p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Denis A. Kuznetsov</p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1817-0126</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сизикова</surname><given-names>Т. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Sizikova</surname><given-names>T. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сизикова Татьяна Евгеньевна, канд. биол. наук </p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Tatiana E. Sizikova, Cand. Sci. (Biol.) </p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5175-916X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Савенко</surname><given-names>С. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Savenko</surname><given-names>S. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Савенко Сергей Вадимович, канд. мед. наук </p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Sergey V. Savenko, Cand. Sci. (Med.) </p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0009-0599-4896</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Яновская</surname><given-names>К. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Yanovskaya</surname><given-names>K. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Яновская Кристина Ивановна</p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Kristina I. Yanovskaya </p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2309-3572</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Овчинников</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Ovchinnikov</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Овчинников Александр Викторович, канд. техн. наук, ст. науч. сотр. </p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Aleksander V. Ovchinnikov, Cand. Sci. (Tech.), Senior Res. </p><p>11 Oktyabrskaya St., Sergiev Posad-6, Moscow Region 141306</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2969-2402</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Миронов</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Mironov</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Миронов Александр Николаевич, д-р мед. наук, проф. </p><p>ул. Октябрьская, д. 11, г. Сергиев Посад-6, Московская область, 141306</p></bio><bio xml:lang="en"><p>Alexander N. Mironov, Dr. Sci. (Med.), Prof.</p><p>31/5 Lomonosovsky Prosp., Moscow 119192</p></bio><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное учреждение «48 Центральный научно-исследовательский институт» Министерства обороны Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>48&lt;sup&gt;th&lt;/sup&gt; Central Scientific Research Institute</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Общество с ограниченной ответственностью «Национальное Агентство Лекарственных Средств»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Agency for Medicines</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>19</day><month>12</month><year>2025</year></pub-date><volume>25</volume><issue>4</issue><fpage>376</fpage><lpage>388</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Борисевич С.В., Рубцов В.В., Писцов М.Н., Логинова С.Я., Кротков В.Т., Сахаров Р.В., Кузнецов Д.А., Сизикова Т.Е., Савенко С.В., Яновская К.И., Овчинников А.В., Миронов А.Н., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Борисевич С.В., Рубцов В.В., Писцов М.Н., Логинова С.Я., Кротков В.Т., Сахаров Р.В., Кузнецов Д.А., Сизикова Т.Е., Савенко С.В., Яновская К.И., Овчинников А.В., Миронов А.Н.</copyright-holder><copyright-holder xml:lang="en">Borisevich S.V., Rubtsov V.V., Pistsov M.N., Loginova S.Y., Krotkov V.T., Sakharov R.V., Kuznetsov D.A., Sizikova T.E., Savenko S.V., Yanovskaya K.I., Ovchinnikov A.V., Mironov A.N.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.biopreparations.ru/jour/article/view/675">https://www.biopreparations.ru/jour/article/view/675</self-uri><abstract><sec><title>ВВЕДЕНИЕ</title><p>ВВЕДЕНИЕ. Перспективным направлением постэкспозиционной профилактики бешенства является применение препаратов на основе моноклональных антител (МкАТ). В связи с отсутствием на фармацевтическом рынке российских препаратов МкАТ для профилактики бешенства целесообразно проведение доклинической оценки защитной эффективности комбинированного препарата на основе докаравимаба и миромавимаба против циркулирующих на территории Российской Федерации уличных штаммов вируса бешенства.</p></sec><sec><title>ЦЕЛЬ</title><p>ЦЕЛЬ. Исследование защитной эффективности комбинированного препарата антирабических моноклональных антител докаравимаба и миромавимаба в отношении актуальных для Российской Федерации штаммов классического вируса бешенства в эксперименте на мышах BALB/с.</p></sec><sec><title>МАТЕРИАЛЫ И МЕТОДЫ</title><p>МАТЕРИАЛЫ И МЕТОДЫ. В качестве тестируемого препарата использовали комбинированный препарат антирабических МкАТ докаравимаба и миромавимаба, в качестве препарата сравнения — иммуноглобулин антирабический Ребинолин. Применяли уличные штаммы вируса бешенства: 777-М, Россия/Самара/2018, RABV/Russia/SP48SolMak/2020; фиксированный штамм CVS. При изучении эффективности использовали 960 мышей линии BALB/с (480 самок, 480 самцов), сформировав 23 группы по 20 животных в каждой (10 самцов, 10 самок). Мышей групп № 3–18 внутримышечно инфицировали вирусом бешенства, а через 6 или 24 ч внутримышечно вводили комбинированный препарат или препарат сравнения. Мышам групп № 1 и 2 вводили 0,9% раствор натрия хлорида (плацебо). Мыши групп № 19–22 служили контролем дозы вируса, а группы № 23 — интактным контролем. Для оценки защитной эффективности препарата проводили взвешивание мышей, определяли инкубационный и клинический периоды, показатели средней продолжительности жизни мышей до гибели, показатели защиты животных от проявления клинических признаков и от гибели. Оценку инфекционной активности вируса проводили на мышах BALB/с при интрацеребральном инфицировании. Специфичность гибели животных подтверждали с помощью ОТ-ПЦР-РВ.</p></sec><sec><title>РЕЗУЛЬТАТЫ</title><p>РЕЗУЛЬТАТЫ. Введение мышам комбинированного препарата на основе докаравимаба и миромавимаба приводило к достоверному увеличению массы тела, средней продолжительности жизни и защите от клинических проявлений бешенства у инфицированных мышей по сравнению с группами контроля дозы вируса. Комбинированный препарат демонстрировал высокую защитную эффективность в отношении штаммов вируса бешенства и не уступал по эффективности препарату сравнения. Введение комбинированного препарата через 6 ч после инфицирования (штаммы 777-М, Россия/Самара/2018, RABV/Russia/SP48SolMak/2020, CVS) обеспечивало защиту от гибели 90–100% самцов и самок мышей, а через 24 ч — 90–100% самцов и 96–100% самок мышей.</p></sec><sec><title>ВЫВОДЫ</title><p>ВЫВОДЫ. В эксперименте на мышах установлена высокая защитная эффективность комбинированного препарата на основе докаравимаба и миромавимаба против актуальных для Российской Федерации уличных штаммов классического вируса бешенства. Комбинированный препарат не уступал по защитной эффективности препарату сравнения, что позволяет его рекомендовать для дальнейших доклинических и клинических исследований.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title> </title><p> </p></sec><sec><title>INTRODUCTION</title><p>INTRODUCTION. Medicinal products based on monoclonal antibodies (mAbs) is one of the promising options for post-exposure rabies prophylaxis. Since Russian pharmaceutical market does not offer anti-rabies mAbs, a combined docaravimab and miromavimab preparation requires a preclinical study of its protective properties against street strains of the rabies virus circulating in the Russian Federation. In this regard, the need to conduct experimental studies is urgent in order to substantiate the efficacy of such products.</p></sec><sec><title>AIM</title><p>AIM. This study aimed to investigate protective efficacy of the combined anti-rabies mAb preparation of docaravimab and miromavimab against the classical rabies virus in BALB/c mice.</p></sec><sec><title>MATERIALS AND METHODS</title><p>MATERIALS AND METHODS. A combination of anti-rabies mAbs, docaravimab and miroma-­vimab, was used as a test drug, while anti-rabies immunoglobulin Rebinolin served as a comparator drug. Street rabies virus strains were used: 777-M, Russia/Samara/2018, RABV/Russia/SP48SolMak/2020, and fixed CVS strain. In the efficacy study, 960 BALB/c mice (480 females, 480 males) were used, forming 23 groups of 20 animals each (10 males and 10 females). Mice groups 3–18 were intramuscularly infected with the rabies virus, and after 6 or 24 hours, either docaravimab and miromavimab combination or a comparator drug (Rebinolin) was administered intramuscularly. Mice from group 1 and 2 were injected with 0.9% sodium chloride solution (placebo). Mice from groups 19–22 served as a dose control for the virus; group 23 served as an intact control. To assess protective properties, mice were weighed; incubation and clinical period, average life span, and protection from clinical manifestations and death was determined. Virus infectivity was evaluated on BALB/c mice after their intracerebral infection. The specific cause of animal death was confirmed using real-time reverse transcriptase polymerase chain reaction.</p></sec><sec><title>RESULTS</title><p>RESULTS. A combined preparation based on anti-rabies mAbs docaravimab and miromavimab resulted in a significantly increased body weight, average life span, and protection from clinical rabies manifestations in infected mice compared with rabies virus dose control groups. The combined preparation demonstrated high protective efficacy against rabies virus strains, not inferior to that of the comparator. Administration of the combined preparation to mice 6 hours after infection (strains 777-M, Russia/Samara/2018, RABV/Russia/SP48SolMak/2020, CVS) showed 90–100% protection of male and female mice against death; after 24 hours — 90–100% of male and 96–100% of female mice.</p></sec><sec><title>CONCLUSIONS</title><p>CONCLUSIONS. An experiment in mice shows high protective efficacy of a combined docaravimab and miromavimab preparation against street strains of the classic rabies virus relevant to the Russian Federation. Protective efficacy of the combined preparation is not inferior to the comparator, thus warranting further preclinical and clinical studies.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>докаравимаб</kwd><kwd>миромавимаб</kwd><kwd>комбинированный препарат</kwd><kwd>моноклональные антитела</kwd><kwd>бешенство</kwd><kwd>классический вирус бешенства</kwd><kwd>Ребинолин</kwd><kwd>мыши BALB/с</kwd><kwd>защитная эффективность</kwd><kwd>постэкспозиционная профилактика бешенства</kwd></kwd-group><kwd-group xml:lang="en"><kwd>docaravimab</kwd><kwd>miromavimab</kwd><kwd>combined preparation</kwd><kwd>monoclonal antibodies</kwd><kwd>mAbs</kwd><kwd>rabies</kwd><kwd>classical rabies virus</kwd><kwd>Rebinolin</kwd><kwd>BALB/c mice</kwd><kwd>protective efficiency</kwd><kwd>post-exposure prophylaxis of rabies</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена в рамках исследования защитной эффективности комбинированного препарата антирабических моноклональных антител докаравимаба и миромавимаба, спонсируемого ООО «Национальное Агентство Лекарственных Средств».</funding-statement><funding-statement xml:lang="en">The research was carried out as part of a study on the protective efficacy of the combined anti-rabies monoclonal antibody docaravimab and miromavimab preparation, sponsored by the National Agency for Medicines.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Снегирева ИИ, Романов БК, Озерецковский НА. 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