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<article 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" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Problems of Virology</journal-id><journal-title-group><journal-title xml:lang="en">Problems of Virology</journal-title><trans-title-group xml:lang="ru"><trans-title>Вопросы вирусологии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0507-4088</issn><issn publication-format="electronic">2411-2097</issn><publisher><publisher-name xml:lang="en">Central Research Institute for Epidemiology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">561</article-id><article-id pub-id-type="doi">10.36233/0507-4088-75</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>ORIGINAL RESEARCHES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Optimization of rabies (Rhabdoviridae: Lyssavirus) dog vaccination schedule using a mathematical model</article-title><trans-title-group xml:lang="ru"><trans-title>Оптимизация схемы вакцинации собак против бешенства (Rhabdoviridae: Lyssavirus) при помощи математической модели</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9757-784X</contrib-id><name-alternatives><name xml:lang="en"><surname>Lobanova</surname><given-names>V. A.</given-names></name><name xml:lang="ru"><surname>Лобанова</surname><given-names>В. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><bold>Varvara A. Lobanova,</bold> Postgraduate Student of the Immunology Department; Assistant Professor of Biotechnology</p><p>141142, Moscow Region, Shchelkovsky district, Biokombinat vill., Russia</p><p>127434, Moscow, Russia</p></bio><bio xml:lang="ru"><p><bold>Лобанова Варвара Андреевна, </bold>аспирант отдела иммунологии; ассистент кафедры биотехнологии</p><p>141142, Московская область, Щёлковский р-н, пос. Биокомбината, Россия</p><p>127434, Москва, Россия</p></bio><email>varvara.ustinova1995@gmail.com</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4295-1424</contrib-id><name-alternatives><name xml:lang="en"><surname>Klyukina</surname><given-names>V. I.</given-names></name><name xml:lang="ru"><surname>Клюкина</surname><given-names>В. И.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>141142, Moscow Region, Shchelkovsky district, Biokombinat vill., Russia</p></bio><bio xml:lang="ru"><p>141142, Московская область, Щёлковский р-н, пос. Биокомбината, Россия</p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">FSBI «All-Russian Research and Technological Institute of Biological Industry»</institution></aff><aff><institution xml:lang="ru">ФГБНУ «Всероссийский научно-исследовательский и технологический институт биологической промышленности»</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">FSBEI HE «Russian State Agrarian University – Moscow Timiryazev Agricultural Academy»</institution></aff><aff><institution xml:lang="ru">ФГБОУ ВО «Российский государственный аграрный университет – МСХА имени К.А. Тимирязева»</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2021-11-04" publication-format="electronic"><day>04</day><month>11</month><year>2021</year></pub-date><volume>66</volume><issue>5</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>354</fpage><lpage>367</lpage><history><date date-type="received" iso-8601-date="2021-11-04"><day>04</day><month>11</month><year>2021</year></date><date date-type="accepted" iso-8601-date="2021-11-04"><day>04</day><month>11</month><year>2021</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2021, Lobanova V.A., Klyukina V.I.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2021, Лобанова В.А., Клюкина В.И.</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="en">Lobanova V.A., Klyukina V.I.</copyright-holder><copyright-holder xml:lang="ru">Лобанова В.А., Клюкина В.И.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://virusjour.crie.ru/jour/article/view/561">https://virusjour.crie.ru/jour/article/view/561</self-uri><abstract xml:lang="en"><p><bold>Introduction. </bold>Most cases of human rabies are caused by dog (Canis lupus familiaris) bites. Therefore, the implementation of vaccination programs of these animals is one of the urgent tasks.</p><p><bold>The work aims</bold> to identify the factors influencing the production of antirabies virus-neutralizing antibodies (VNAs) in vaccinated dogs, and to formulate recommendations for adjusting the vaccination schedule using mathematical modeling (MM).</p><p><bold>Material and methods.</bold> We used a fixed-effects modeling procedure to estimate the two-compartment model parameters using log-transformed data (obtained by RFFIT, rapid fluorescent focus inhibition test; and FAVN, fluorescent antibody virus-neutralization test) on the VNAs levels in the serum of vaccinated dogs.</p><p><bold>Results.</bold> More vigorous immune response after a two-dose primary vaccination is formed in juvenile dogs at the age of 3 months to 1 year compared to the adult dogs. Following the primary vaccination and revaccination 1 year after, VNAs were produced more intensively in adult stray dogs than in domestic dogs.</p><p><bold>Discussion.</bold> The short-term immune response observed in dogs aged up to 3 months is due to the presence of colostral antibodies and the active growth of the organism at this age. The results of our study confirm that most of the dogs have a level of antirabies VNAs of ≥0.5 IU/ml up to two or more years following immunization. However, only regular annual revaccination ensures the protective VNAs level in animals that responded poorly to vaccination due to various factors.</p><p><bold>Conclusion.</bold> The following antirabies vaccination schedule is recommended: primary vaccination of the dog at the age of 3 months up to 1 year with 1–2 month intervals, then revaccination annually. This work also demonstrates the possibility of a wider application of MM methods for solving problems of vaccine prevention.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Введение. </bold>Большинство случаев бешенства (Rhabdoviridae: Lyssavirus) у людей вызвано укусами домашних и диких собак (Canis lupus familiaris). В этой связи одной из актуальных задач является организация программ массовой вакцинации этих животных.</p><p><bold>Цель работы</bold> – выявить факторы, влияющие на синтез вируснейтрализующих антител (ВНА) к вирусу бешенства у вакцинированных собак, сформировать рекомендации по корректировке схемы вакцинации с использованием методов математического моделирования (ММ).</p><p><bold>Материал и методы. </bold>Разработана двухкомпартментная математическая модель, параметры которой откалиброваны на лог-трансформированных данных о содержании ВНА в сыворотке крови вакцинированных собак с использованием нелинейного моделирования с фиксированными эффектами. Результаты получены методами RFFIT (rapid fluorescent focus inhibition test, анализ быстрого ингибирования фокусов флюоресценции) и FAVN (fluorescent antibody virus-neutralization test, тест нейтрализации вируса флюоресцентными антителами).</p><p><bold>Результаты. </bold>Установлено, что при двукратной первичной вакцинации у щенков в возрасте от 3 мес до 1 года формируется более напряжённый иммунный ответ по сравнению с таковым у взрослых особей. При первичной вакцинации и ревакцинации спустя 1 год и более ВНА у взрослых уличных собак синтезируются более интенсивно, чем у домашних.</p><p><bold>Обсуждение. </bold>Менее длительный иммунный ответ у животных, вакцинированных в возрасте до 3 мес, объясняется как наличием колостральных антител, так и активным развитием организма в этот период. Результаты наших исследований и данные работ других авторов подтверждают наличие у большинства собак протективного уровня ВНА к вирусу бешенства ≥0,5 МЕ/мл на протяжении 2 и более лет после вакцинации. Однако лишь регулярная ежегодная ревакцинация способствует достижению и поддержанию этого показателя у особей, плохо отвечающих на вакцинацию в силу различных факторов.</p><p><bold>Заключение.</bold> Рекомендована следующая схема вакцинации собак против бешенства: первичное введение вакцинного препарата в возрасте от 3 мес до 1 года с 1–2-месячным интервалом, в дальнейшем ежегодная ревакцинация. Настоящая работа демонстрирует возможность более широкого применения методов ММ для решения задач вакцинопрофилактики.</p></trans-abstract><kwd-group xml:lang="en"><kwd>rabies</kwd><kwd>prevention and control</kwd><kwd>virus-neutralizing antibodies</kwd><kwd>vaccination</kwd><kwd>mathematical modeling</kwd><kwd>nonlinear modeling</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>бешенство</kwd><kwd>профилактика</kwd><kwd>вируснейтрализующие антитела</kwd><kwd>вакцинация</kwd><kwd>математическое моделирование</kwd><kwd>нелинейное моделирование</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>1. United Against Rabies Collaboration. First annual progress report: Global Strategic Plan to End Human Deaths from Dog-mediated Rabies by 2030. Geneva; 2019. 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