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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="research-article" 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">16611</article-id><article-id pub-id-type="doi">10.36233/0507-4088-222</article-id><article-id pub-id-type="edn">mcackf</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>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Immune reactivity of two biological models to vaccination with inactivated vaccine QazVac against coronavirus infection COVID-19</article-title><trans-title-group xml:lang="ru"><trans-title>Иммунная реактивность двух биологических моделей на прививку инактивированной вакциной QazVac против коронавирусной инфекции COVID-19</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4141-7174</contrib-id><name-alternatives><name xml:lang="en"><surname>Myrzakhmetova</surname><given-names>Balzhan Sh.</given-names></name><name xml:lang="ru"><surname>Мырзахметова</surname><given-names>Балжан Шайзадаевна</given-names></name></name-alternatives><address><country country="KZ">Kazakhstan</country></address><bio xml:lang="en"><p>Candidate of Biological Sciences, Head of the Especially Dangerous Infectious Diseases Laboratory</p></bio><bio xml:lang="ru"><p>канд. биол. наук,<bold> </bold>заведующая лабораторией «Особо опасные инфекционные заболевания»</p></bio><email>balzhan.msh@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5382-831X</contrib-id><name-alternatives><name xml:lang="en"><surname>Zhapparova</surname><given-names>Gulzhan A.</given-names></name><name xml:lang="ru"><surname>Жаппарова</surname><given-names>Гульжан Амировна</given-names></name></name-alternatives><address><country country="KZ">Kazakhstan</country></address><bio xml:lang="en"><p>Master of Biology, Senior Researcher of the Especially Dangerous Infectious Diseases Laboratory</p></bio><bio xml:lang="ru"><p>магистр биологии, старший научный сотрудник лаборатории «Особо опасные инфекционные заболевания»</p></bio><email>gulzhan1003@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5788-6074</contrib-id><name-alternatives><name xml:lang="en"><surname>Bisenbayeva</surname><given-names>Karina B.</given-names></name><name xml:lang="ru"><surname>Бисенбаева</surname><given-names>Карина Бисенбаевна</given-names></name></name-alternatives><address><country country="KZ">Kazakhstan</country></address><bio xml:lang="en"><p>Master of Biology, Junior Researcher of the Especially Dangerous Infectious Diseases Laboratory</p></bio><bio xml:lang="ru"><p>магистр биологии, младший научный сотрудник лаборатории «Особо опасные инфекционные заболевания»</p></bio><email>bisenbayeva.karina@bk.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0004-9526-3539</contrib-id><name-alternatives><name xml:lang="en"><surname>Toytanova</surname><given-names>Aizhan S.</given-names></name><name xml:lang="ru"><surname>Тойтанова</surname><given-names>Айжан Сейткаримовна</given-names></name></name-alternatives><address><country country="KZ">Kazakhstan</country></address><bio xml:lang="en"><p>Master of Biology, Junior Researcher of the Especially Dangerous Infectious Diseases Laboratory</p></bio><bio xml:lang="ru"><p>магистр биологии, младший научный сотрудник лаборатории «Особо опасные инфекционные заболевания»</p></bio><email>aizhana-1308@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6565-082X</contrib-id><name-alternatives><name xml:lang="en"><surname>Tuyskanova</surname><given-names>Moldir S.</given-names></name><name xml:lang="ru"><surname>Туысканова</surname><given-names>Молдир Сежанкызы</given-names></name></name-alternatives><address><country country="KZ">Kazakhstan</country></address><bio xml:lang="en"><p>Master of Pedagogical Sciences (Biology), Junior Researcher of the Collection of Microorganisms Laboratory</p></bio><bio xml:lang="ru"><p>магистр педагогических наук по специальности биология, младший научный сотрудник лаборатории «Коллекция микроорганизмов»</p></bio><email>monica_94@list.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4238-5116</contrib-id><name-alternatives><name xml:lang="en"><surname>Zhugunissov</surname><given-names>Kuandyk D.</given-names></name><name xml:lang="ru"><surname>Жугунисов</surname><given-names>Куандык Даулетбаевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>PhD, Head of the Collection of Microorganisms Laboratory</p></bio><bio xml:lang="ru"><p>PhD, заведующий лабораторией «Коллекция микроорганизмов»</p></bio><email>kuandyk_83@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8481-0673</contrib-id><name-alternatives><name xml:lang="en"><surname>Kutumbetov</surname><given-names>Lespek B.</given-names></name><name xml:lang="ru"><surname>Кутумбетов</surname><given-names>Леспек Бекболатович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Doctor of Veterinary Sciences, Professor, Chief Researcher of the Especially Dangerous Infectious Diseases Laboratory</p></bio><bio xml:lang="ru"><p>д-р вет. наук, профессор, главный научный сотрудник лаборатории «Особо опасные инфекционные заболевания»</p></bio><email>lespek.k@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Research Institute for Biological Safety Problems</institution></aff><aff><institution xml:lang="ru">РГП «Научно-исследовательский институт проблем биологической безопасности» МЗ РК</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2024-07-05" publication-format="electronic"><day>05</day><month>07</month><year>2024</year></pub-date><volume>69</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>219</fpage><lpage>230</lpage><history><date date-type="received" iso-8601-date="2024-01-30"><day>30</day><month>01</month><year>2024</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, Myrzakhmetova B.S., Zhapparova G.A., Bisenbayeva K.B., Toytanova A.S., Tuyskanova M.S., Zhugunissov K.D., Kutumbetov L.B.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2024, Мырзахметова Б.Ш., Жаппарова Г.А., Бисенбаева К.Б., Тойтанова А.С., Туысканова М.С., Жугунисов К.Д., Кутумбетов Л.Б.</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">Myrzakhmetova B.S., Zhapparova G.A., Bisenbayeva K.B., Toytanova A.S., Tuyskanova M.S., Zhugunissov K.D., Kutumbetov L.B.</copyright-holder><copyright-holder xml:lang="ru">Мырзахметова Б.Ш., Жаппарова Г.А., Бисенбаева К.Б., Тойтанова А.С., Туысканова М.С., Жугунисов К.Д., Кутумбетов Л.Б.</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/16611">https://virusjour.crie.ru/jour/article/view/16611</self-uri><abstract xml:lang="en"><p><bold>Introduction. </bold>Specific prevention of a number of infectious diseases has been introduced into the vaccination schedule. The production of immunoprophylactic drugs, in order to establish standard properties, including safety and specific effectiveness, requires strict adherence to manufacturing regulations, and the reliability of the results obtained requires monitoring of these parameters. The specific effectiveness of vaccine preparations is standardized according to the indicators of stimulation of specific antibody response formed in the body of vaccinated model biological objects.</p> <p><bold>Objective. </bold>Determination of the immune reactivity of white mice to vaccination with the QazVac vaccine to establish the possibility of using them as a biological model in assessing the immunogenicity of the vaccine instead of Syrian hamsters.</p> <p><bold>Materials and methods. </bold>The immune reactivity of model animals was assessed by the seroconversion rate, dynamics of antibody titers to the SARS-CoV-2 virus formed in the body after vaccination with the test vaccine. In the case of seropositivity of animals before administration of vaccine or placebo, the level of immune reactivity was calculated by the difference in antibody titers between control and vaccinated animals or by the difference in antibody titers before and after immunization. Specific antibodies were detected and their titer was determined using a neutralization reaction.</p> <p><bold>Results. </bold>The research results showed that the tested biological models had approximately the same immune reactivity to the administration of the QazVac vaccine, confirmed by the level and dynamics of antibody titers. When analyzing the fold increase in antibody titers in comparison to those of control animals, Syrian hamsters were more reactive compared to mice. But SPF white mice were standardized in their lack of the immune reactivity to SARS-CoV-2 virus before the immunization.</p> <p><bold>Conclusion. </bold>The data obtained indicate that the immune reactivity of white mice to the administration of the QazVac vaccine in terms of the rate and dynamics of the formation of virus-neutralizing antibodies is approximately equivalent to the immune reactivity of Syrian hamsters. Before immunization with the vaccine, SPF white mice, in contrast to Syrian hamsters, do not have humoral immunity specific to the SARS-CoV-2 virus. The immune reactivity equivalent to that observed of Syrian hamsters and the absence of antibodies to the SARS-CoV-2 virus at a baseline indicate the superiority of the use of white mice in assessing the immunogenicity of vaccines against COVID-19 and/or obtaining specific factors of humoral immunity.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Введение. </bold>Специфическая профилактика ряда инфекционных болезней введена в календарь медицинских прививок. Производство иммунопрофилактических препаратов в целях установления стандартных свойств, в том числе по безопасности и специфической эффективности, требует строгого соблюдения регламента изготовления, а достоверность полученных результатов – проведения контроля указанных параметров. Специфическую эффективность вакцинных препаратов стандартизируют по показателям стимуляции гуморальных факторов иммунитета, формируемых в организме привитых модельных биологических объектов.</p> <p><bold>Цель работы. </bold>Определение иммунной реактивности белых мышей на прививку вакциной QazVac для установления возможности их использования в качестве биологической модели в оценке иммуногенности вакцины вместо сирийских хомяков.</p> <p><bold>Материалы и методы. </bold>Оценку иммунной реактивности модельных животных проводили по количеству сероконверсивности, скорости и динамике титров антител на вирус SARS-CoV-2, формируемых в организме после прививки испытуемой вакциной.</p> <p><bold>Результаты. </bold>Результаты исследований показали, что испытуемые биологические модели обладают примерно одинаковой иммунной реактивностью на введение вакцины QazVac, подтверждающим свидетельством которой являлись уровень и динамика титров антител. При анализе кратности увеличения титров антител в сравнении с таковыми контрольных животных, сирийские хомяки обладают сравнительно большей реактивностью. Но белые мыши, свободные от патогенной микрофлоры (СПФ), стандартны по интактности от антител на вирус SARS-CoV-2.</p> <p><bold>Заключение. </bold>Полученные данные свидетельствует о том, что иммунная реактивность белых мышей на введение вакцины QazVac по скорости и динамике формирования вируснейтрализующих антител является практически равнозначной иммунной реактивности сирийских хомяков. В организме белых мышей категории СПФ до прививки вакциной, в отличие от сирийских хомяков, не содержатся факторы гуморального иммунитета, специфичные к вирусу SARS-CoV-2.</p></trans-abstract><kwd-group xml:lang="en"><kwd>immune reactivity</kwd><kwd>SARS-CoV-2 virus</kwd><kwd>neutralization reaction</kwd><kwd>vaccine</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>иммунная реактивность</kwd><kwd>вирус SARS-CoV-2</kwd><kwd>реакция нейтрализации</kwd><kwd>вакцина</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="en">Ministry of Health of the Republic of Kazakhstan</institution></institution-wrap><institution-wrap><institution xml:lang="ru">Министерство здравоохранения Республики Казахстан</institution></institution-wrap></funding-source></award-group></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Young M., Crook H., Scott J., Edison P. COVID-19: Virology, variants, and vaccines. BMJ Med. 2022; 1(1): e000040. DOI: https://doi.org/10.1136/bmjmed-2021-000040</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Fu Y., Zhao J., Wei X., Han P., Yang L., Ren T., et al. Effectiveness and cost-effectiveness of inactivated vaccine to address COVID-19 pandemic in China: Evidence from randomized control trials and real-world studies. Front. Public Health. 2022; 10: 917732. DOI: https://doi.org/10.3389/fpubh.2022.917732</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Minor P.D. Live attenuated vaccines: Historical successes and current challenges. Virology. 2015; 479-480: 379–92. DOI: https://doi.org/10.1016/j.virol.2015.03.032</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Subbarao K. Live attenuated cold-adapted influenza vaccines. Cold Spring Harb. Perspect. Med. 2021; 11(9): a038653. DOI: https://doi.org/10.1101/cshperspect.a038653</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Okamura S., Ebina H. Could live attenuated vaccines better control COVID-19. Vaccine. 2021; 39(39): 5719–26. DOI: https://doi.org/10.1016/j.vaccine.2021.08.018</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Yarosh O.K., Wandeler A.I., Graham F.L., Campbell J.B., Prevee L. Human adenovirus type 5 vectors expressing rabies glycoprotein. Vaccine. 1996; 14(13): 1257–64. DOI: https://doi.org/10.1016/s0264-410x(96)00012-6</mixed-citation></ref><ref id="B7"><label>7.</label><citation-alternatives><mixed-citation xml:lang="en">Pushko P., Ishmukhametov А.А., Bredenbeek P.P., Lukashevich I.S. Experimental DNA-launched live-attenuated vaccines against yellow fever. Epidemiologiya i vaktsinoprofilaktika. 2019; 18(1): 18–25. DOI: https://doi.org/10.31631/2073-3046-2019-18-1-18-25 EDN: https://elibrary.ru/scwjvy (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Пушко П., Ишмухаметов А.А., Бреденбеек П.Дж., Лукашевич И.С. Экспериментальные живые аттенуированные вакцины против жёлтой лихорадки на основе инфекционных ДНК. Эпидемиология и вакцинопрофилактика. 2019; 18(1): 18–25. DOI: https://doi.org/10.31631/2073-3046-2019-18-1-18-25 EDN: https://elibrary.ru/scwjvy</mixed-citation></citation-alternatives></ref><ref id="B8"><label>8.</label><mixed-citation>Bugybayeva D., Kydyrbayev Z., Zinina N., Assanzhanova N., Yespembetov B., Kozhamkulov Y., et al. A new candidate vaccine for human brucellosis based on influenza viral vectors: a preliminary investigation for the development of an immunization schedule in a guinea pig model. Infect. Dis. Poverty. 2021; 10(1): 13. DOI: https://doi.org/10.1186/s40249-021-00801-y</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>McMenamin M.E., Cowling B.J. CoronaVac efficacy data from Turkey. Lancet. 2021; 398(10314): 1873–4. DOI: https://doi.org/10.1016/S0140-6736(21)02288-1</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Heidary M., Kaviar V.H., Shirani M., Ghanavati R., Motahar M., Sholeh M., et al. A comprehensive review of the protein subunit vaccines against COVID-19. Front. Microbiol. 2022; 13: 927306. DOI: https://doi.org/10.3389/fmicb.2022.927306</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Bennett J.V., De Castro L.J., Valdespino-Gomez J.L., Garcia-Garcia Mde L., Islas-Romero R., Echaniz-Aviles G., et al. Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responces than injected vaccines: randomized trials in Mexican schoolchildren. Bull. World Health Organ. 2002; 80(10): 806–12.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Ecunwe E.O. Immunization by inhalation of aerosolized measles vaccine. Ann. Trop. Ped. 1990; 10(2): 145–9. DOI: https://doi.org/10.1080/02724936.1990.11747422</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Liashenko V.A., Krasnova V.P., Youminova N.V. Measles IgA in the nasal washings of adult volunteers and children immunized intranasally with measles vaccine L-16. Hum. Antibodies. 1999; 9(3): 143–8.</mixed-citation></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">Bektimirov T.A. Successes of vaccination of measles, rubella and mumps abroad. Vaktsinatsiya. 2006; (4): 4–5. (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Бектимиров Т.А. Успехи вакцинопрофилактики кори, краснухи и эпидемического паротита за рубежом. Вакцинация. 2006; (4): 4–5.</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><citation-alternatives><mixed-citation xml:lang="en">Unasova T.N., Binyatova A.S., Phadeykina O.V., Sarkisyan K.A., Movsesyants A.A., Ignatyev G.M., et al. Analysis of the quality of national vaccine against Rubella. Voprosy virusologii. 2018; 63(2): 90–6. DOI: https://doi.org/10.18821/0507-4088-2018-63-2-90-96 EDN: https://elibrary.ru/yuujuh (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Юнасова Т.Н., Бинятова А.С., Федейкина О.В., Саркисян К.А., Мовсесянц А.А., Игнатьев Г.М. и др. Анализ качества отечественной вакцины для профилактики краснухи. Вопросы вирусологии. 2018; 63(2): 90–6. DOI: https://doi.org/10.18821/0507-4088-2018-63-2-90-96 EDN: https://elibrary.ru/yuujuh</mixed-citation></citation-alternatives></ref><ref id="B16"><label>16.</label><citation-alternatives><mixed-citation xml:lang="en">Shamsutdinova O.A. Live attenuated vaccines for the immunoprophylaxis. Infektsiya i immunitet. 2017; 7(2): 107–16. DOI: https://doi.org/10.15789/2220-7619-2017-2-107-116 EDN: https://elibrary.ru/ysktdf (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Шамсутдинова О.А. Живые аттенуированные вакцины для иммунопрофилактики. Инфекция и иммунитет. 2017; 7(2): 107–16. DOI: https://doi.org/10.15789/2220-7619-2017-2-107-116 EDN: https://elibrary.ru/ysktdf</mixed-citation></citation-alternatives></ref><ref id="B17"><label>17.</label><mixed-citation>Vanaparthy R., Mohan G., Vasireddy D., Atluri P. Review of COVID-19 viral vector-based vaccines and COVID-19 variants. Infez. Med. 2021; 29(3): 328–38. DOI: https://doi.org/10.53854/liim-2903-3</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Logunov D.Y., Dolzhikova I.V., Zubkova O.V., Tukhvatullin A.I., Shcheblyakov D.V., Dzharullaeva A.S., et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet. 2020; 396(10255): 887–97. DOI: https://doi.org/10.1016/s0140-6736(20)31866-3</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Khoshnood S., Arshadi M., Akrami S., Koupaei M., Ghahramanpour H., Shariati A., et al. An overview on inactivated and live-attenuated SARS-CoV-2 vaccines. J. Clin. Lab. Anal. 2022; 36(5): e24418. DOI: https://doi.org/10.1002/jcla.24418</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Zakarya K., Kutumbetov L., Orynbayev M., Abduraimov Y., Sultankulova K., Kassenov M., et al. Safety and immunogenicity of a QazCovid-in® inactivated whole-virion vaccine against COVID-19 in healthy adults: A single-centre, randomised, single-blind, placebo-controlled phase 1 and an open-label phase 2 clinical trials with a 6 months follow-up in Kazakhstan. EClinicalMedicine. 2021; 39: 101078. DOI: https://doi.org/10.1016/j.eclinm.2021.101078</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Khairullin B., Zakarya K., Orynbayev M., Abduraimov Y., Kassenov M., Sarsenbayeva G., et al. Efficacy and safety of an inactivated whole-virion vaccine against COVID-19, QazCovid-in®, in healthy adults: A multicentre, randomised, single blind, placebo-controlled phase 3 clinical trial with a 6-month follow-up. EClinicalMedicine. 2022; 50: 101526. DOI: https://doi.org/10.1016/j.eclinm.2022.101526</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Nabirova D., Horth R., Smagul M., Nukenova G., Yesmagambetova A., Singer D., et al. Effectiveness of four vaccines in preventing SARS-CoV-2 infection in Almaty, Kazakhstan in 2021: retrospective population-based cohort study. Front. Public Health. 2023; 11: 1205159. DOI: https://doi.org/10.3389/fpubh.20231205159</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Zhugunissov K., Zakarya K., Khairullin B., Orynbayev M., Abduraimov Y., Kassenov M., et al. Development of the inactivated QazCovid-in vaccine: protective efficacy of the vaccine in Syrian hamsters. Front. Microbiol. 2021; 12: 720437. DOI: https://doi.org/10.3389/fmicb.2021.720437</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Nurpeisova A., Khairullin B., Abitaev R., Shorayeva K., Jekebekov K., Kalimolda E., et al. Safety and immunogenicity of the first Kazakh inactivated vaccine for COVID-19. Hum. Vaccin. Immunother. 2022; 18(5): 2087412. DOI: https://doi.org/10.1080.21645515.2022.2087412.</mixed-citation></ref><ref id="B25"><label>25.</label><citation-alternatives><mixed-citation xml:lang="en">Zhugunissov K., Kerimbayev A.A., Kopeev S., Myrzakhmetova B., Tuyskanova M., Nakhanov A., et al. SARS-CoV-2 Virus: isolation, growth, thermostability, inactivation and passages. Vestnik KazNU. Seriya biologicheskaya. 2022; 90(1): 73–89. DOI: https://doi.org/10.26577/eb.2022.v90.il.07 (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Жугунисов К.Д., Керимбаев А.А., Копеев С.К., Мырзахметова Б.Ш., Туысканова М.С., Наханов А.К. и др. Вирус SARS-CoV-2: выделение, культивирование, термостабильность, инактивация и пассирование. Вестник КазНУ. Серия биологическая. 2022; 90(1): 73–89. DOI: https://doi.org/10.26577/eb.2022.v90.il.07</mixed-citation></citation-alternatives></ref><ref id="B26"><label>26.</label><mixed-citation>Imai M., Iwatsuki-Horimoto K., Hatta M., Loeher S., Halfmann P.J., Nakajima N., et al. Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development. Proc. Natl Acad. Sci. USA. 2020: 117(28): 16587–95. DOI: https://doi.org//10.1073/pnas.2009799117</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Kim Y.I., Kim S.G., Kim S.M., Kim E.H., Park S.J., Yu K.M., et al. Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host Microbe. 2020: 27(5): 704–9.e2. DOI: https://doi.org/10.1016/j.chom.2020.03.023</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Bao L., Deng W., Huang B., Gao H., Liu J., Ren L., et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature. 2020; 583(7818): 830–3. DOI: https://doi.org/10.1038/s41586-020-2312-y</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Sun S.H., Chen O., Gu H.J., Yang G., Wang Y.X., Huang X.Y., et al. A mouse model of SARS-CoV-2 infection and pathogenesis. Cell Host Microbe. 2020; 28(1): 124–33.e4. DOI: https://doi.org/10.1016/j.chom.2020.05.020</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Soldatov V.O., Kubekina M.V., Silaeva Y.Yu., Bruter A.V., Deykin A.V. On the way from SARS-CoV-2 sensitive mice to murine COVID-19 model. Res. Results Pharmacol. 2020; 6(2): 1–7. DOI: https://doi.org/10.3897/rrpharmacology.6.53633</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Schlottau K., Rissmann M., Graaf A., Schön J., Sehl J., Wylezich C., et al. SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens an experimental transmission study. Lancet Microbe. 2020; 1(5): e218–25. DOI: https://doi.org/10.1016/S2666-5247(20)30089-6</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Richard M., Kok A., de Meulder D., Bestebroer T.M., Lamers M.M., Okba N.M.A., et al. SARS-CoV-2 is transmitted via contact and via the air between ferrets. Nat. Commun. 2020; 11(1): 3496. DOI: https://doi.org/10.1038/s41467-020-17367-2</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Chan J.F., Zhang A.J., Yuan S., Poon V.K., Chan C.C., Lee A.C., et al. Simulation of the clinical and pathological manifestations of Coronavirus Disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility. Clin. Infect. Dis. 2020; 71(9): 2428–46. DOI: https://doi.org/10.1093/cid/ciaa325</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Boudewijns R., Thibaut H.J., Kaptein S.J.F., Li R., Vergote V., Seldeslachts J., et al. STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters. bioRxiv. 2020. Preprint. DOI: https://doi.org/10.1101/2020.04.23.056838</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Sia S.F., Yan L.M., Chin A.W.H., Fung K., Choy K.T., Wong A.Y.L., et al. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature. 2020; 583(7818): 834–8. DOI: https://doi.org/10.1038/s41586-020-2342-5</mixed-citation></ref><ref id="B36"><label>36.</label><citation-alternatives><mixed-citation xml:lang="en">Petrova N.V., Ganina K.K., Tarasov S.A. Susceptibility of animal species to experimental SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) infection. Voprosy virusologii 2021; 66(2): 103–10. DOI: https://doi.org/10.36233/0507-4088-47 EDN: https://elibrary.ru/hfvjns (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Петрова Н.В., Ганина К.К., Тарасов С.А. Изучение чувствительности лабораторных животных к вирусу SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus). Вопросы вирусологии. 2021; 66(2): 103–11. DOI: https://doi.org/10.36233/0507-4088-47 EDN: https://elibrary.ru/hfvjns</mixed-citation></citation-alternatives></ref><ref id="B37"><label>37.</label><mixed-citation>Takayama K. In vitro and Animal Models for SARS-CoV-2 research. Trends Pharmacol. Sci. 2020; 41(8): 513–7. DOI: https://doi.org/10.1016/j.tips.2020.05.005</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Sun J., Zhuang Z., Zheng J., Li K., Wong R.L., Liu D., et al. Generation of a broadly useful model for COVID-19 pathogenesis, vaccination and treatment. Cell. 2020; 182(3): 734–43.e5. DOI: https://doi.org/10.1016/j.cell.2020.06.010</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Golden J.W., Cline C.R., Zeng X., Garrison A.R., Carey B.D., Mucker E.M., et al. Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease. JCI Insight. 2020; 5(19): e142032. DOI: https://doi.org/10.1172/jci.insight.142032</mixed-citation></ref><ref id="B40"><label>40.</label><citation-alternatives><mixed-citation xml:lang="en">Martina B.E., Haagmans B.L., Kuiken T., Fouchier R.A.M., Rimmelzwaan G.F., van Amerongen G., et al. SARS virus infection of cats and ferrets. Nature. 2023; 425(6961): 915. https://doi.org/10.1038/425915a</mixed-citation><mixed-citation xml:lang="ru">Martina B.E., Haagmans B.L., Kuiken T., Fouchier R.A.M., Rimmelzwaan G.F., van Amerongen G., et al. SARS virus infection of cats and ferrets. Nature. 2023; 425(6961): 915. DOI: https://doi.org/10.1038/425915a</mixed-citation></citation-alternatives></ref><ref id="B41"><label>41.</label><citation-alternatives><mixed-citation xml:lang="en">Nagornykh A.M., Tyumentsev A.I., Tyumentseva M.A., Akimkin V.G. SARS, SARS again, and MERS. Review of animal models of human respiratory syndromes caused by coronavirus infections. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2020; 97(5): 431–44. DOI: https://doi.org/10.36233/0372-9311-2020-97-5-6 EDN: https://elibrary.ru/zqdssu (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Нагорных А.М., Тюменцев А.И., Тюменцева М.А., Акимкин В.Г. SARS, снова SARS и MERS. Обзор животных моделей респираторных синдромов человека, вызываемых коронавирусными инфекциями. Журнал микробиологии, эпидемиологии и иммунобиологии. 2020; 97(5): 431–44. DOI: https://doi.org/10.36233/0372-9311-2020-97-5-6 EDN: https://elibrary.ru/zqdssu</mixed-citation></citation-alternatives></ref><ref id="B42"><label>42.</label><mixed-citation>Shi J., Wen Z., Zhong G., Yang H., Wang C., Huang B., et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus-2. Science. 2020; 368(6494): 1016–20. DOI: https://doi.org/10.1126/science.abb7015</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Woolsey C., Borisevich V., Prasad A.N., Agans K.N., Deer D.J., Dobias N.S., et al. Establishment of an African green monkey model for COVID-19. bioRxiv. 2020. Preprint. DOI: https://doi.org/10.1101/2020.05.17.100289</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Corbett K.S., Flynn B., Foulds K.E., Francica J.R., Boyoglu-Barnum S., Werner A.P., et al. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N. Engl. J. Med. 2020; 383(16): 1544–55. DOI: https://doi.org/10.1056/NEJMoa2024671</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Shan C., Yao Y.F., Yang X.L., Zhou Y.W., Gao G., Peng Y., et al. Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in the rhesus macaques. Cell Res. 2020; 30(8): 670–7. DOI: https://doi.org/10.1038/s41422-020-0364-z</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Singh D.K., Ganatra S.R., Singh B., Cole J., Alfson K.J., Clemmons E., et al. SARS-CoV-2 infection leads to acute infection with dynamic cellular and inflammatory flux in the lung that varies across nonhuman primate species. bioRxiv. 2020. Preprint. DOI: https://doi.org/10.1101/2020.06.05.136481</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Williamson B.N., Feldmann F., Schwarz B., Meade-White K., Porter D.P., Schulz J., et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. bioRxiv. 2020. Preprint. DOI: https://doi.org/10.1101/2020.04.15.043166</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Yu J., Tostanoski L.H., Peter L., Mercado N.B., McMahan K., Mahrokhian S.H., et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science. 2020; 369(6505): 806–11. DOI: https://doi.org/10.1126/science.abc6284</mixed-citation></ref><ref id="B49"><label>49.</label><citation-alternatives><mixed-citation xml:lang="en">Myrzakhmetova B.Sh., Zhapparova G.A., Bissenbayeva K.B., Toytanova A.S., Tuyskanova M.S., Nakhanova G.D., et al. Standartization of immunogenicity of inactivated vaccine QazVac against coronavirus infection COVID-19 from an epidemiologically relevant strain. Eurasian Journal of Applied Biotechnology. 2023; (4): 31–41. DOI: https://doi.org/10.11134/btp.4.2023.4 (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Мырзахметова Б.Ш., Жаппарова Г.А., Бисенбаева К.Б., Тойтанова А.С., Туысканова М.С., Наханова Г.Д. и др. Стандартизация иммуногенности инактивированной вакцины QazVac против коронавирусной инфекции COVID-19 из эпидемиологически актуального штамма. Eurasian Journal of Applied Biotechnology. 2023; (4): 31–41. DOI: https://doi.org/10.11134/btp.4.2023.4</mixed-citation></citation-alternatives></ref><ref id="B50"><label>50.</label><mixed-citation>Reed L.J., Muench Simple H.A. Method of estimating fifty per cent endpoints. Am. J. Epidemiol. 1938; 27(3): 493–7. DOI: https://doi.org/10.1093/oxfordjournals.aje.a118408(1938)</mixed-citation></ref><ref id="B51"><label>51.</label><citation-alternatives><mixed-citation xml:lang="en">Myrzagaliev A.K., Shcherbakova I.V. Possibilities of using the Student’s t-test for analyzing medical research data. Byulleten’ meditsinskikh internet-konferentsii. 2014; 4(11): 1275. EDN: https://elibrary.ru/tgglen (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Мырзагалиев А.К., Щербакова И.В. Возможности использования t-критерия Стъюдента для анализа данных медицинских исследований. Бюллетень медицинских интернет-конференций. 2014; 4(11): 1275. EDN: https://elibrary.ru/tgglen</mixed-citation></citation-alternatives></ref><ref id="B52"><label>52.</label><mixed-citation>Guo B., Yuan Y. A comparative review of methods for comparing means using partially paired data. Stat. Methods Med. Res. 2017; 26(3): 1323–40. DOI: https://doi.org/10.1177/0962280215577111</mixed-citation></ref><ref id="B53"><label>53.</label><citation-alternatives><mixed-citation xml:lang="en">Tuyskanova M.S., Zhugunissov K.D., Ozaslan M., Myrzakhmetova B.Sh., Kutumbetov L.B. Clinical symptoms and signs in hamsters during experimental infection with the SARS-CoV-2 virus (Coronaviridae: Betacoronavirus). Voprosy virusologii. 2023; 68(6): 513–25. DOI: https://doi.org/10.36233/0507-4088-202 EDN: https://elibrary.ru/kivlek (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Туысканова М.С., Жугунисов К.Д., Ozaslan M., Мырзахметова Б.Ш., Кутумбетов Л.Б. Клинические симптомы/признаки у хомяков при экспериментальном заражении вирусом SARS-CoV-2 (Coronaviridae: Betacoronavirus). Вопросы вирусологии. 2023; 68(6): 513–25. DOI: https://doi.org/10.36233/0507-4088-202 EDN: https://elibrary.ru/kivlek</mixed-citation></citation-alternatives></ref><ref id="B54"><label>54.</label><mixed-citation>Moore D., McCabe G. Introduction to the Practice of Statistics. New York: Freeman W.H. and Co; 1989.</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Zar J.H. Biostatistical Analysis. Upper Saddle River, N.J.: Prentice Hall; 1999: 43–5.</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Student. The probable error of a mean. Biometrika. 1908; 6(1): 1–25.</mixed-citation></ref><ref id="B57"><label>57.</label><citation-alternatives><mixed-citation xml:lang="en">Khairullin B., Zakarya K., Orynbayev M., Kassenov M., Sultankulova K., Zhugunissov K., et al. Method for obtaining an inactivated vaccine for the prevention of COVID-19. Patent RK № 34761; 2020. (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Хайруллин Б.М., Закарья К.Д., Орынбаев М.Б., Касенов М.М., Султанкулова К.Т., Жугунисов К.Д. и др. Способ получения инактивированной вакцины для профилактики COVID-19. Патент РК № 34761; 2020.</mixed-citation></citation-alternatives></ref><ref id="B58"><label>58.</label><citation-alternatives><mixed-citation xml:lang="en">State Pharmacopoeia of the Republic of Kazakhstan. First edition, issue 1; 2008. (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Государственная Фармакопея Республики Казахстан. Первое издание, выпуск 1; 2008.</mixed-citation></citation-alternatives></ref><ref id="B59"><label>59.</label><citation-alternatives><mixed-citation xml:lang="en">Mironov A.N. Guidelines for Conducting Preclinical Studies of Medicinal Products [Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv.]. Moscow; 2021. (in Russian)</mixed-citation><mixed-citation xml:lang="ru">Миронов А.Н. Руководство по проведению доклинических исследований лекарственных средств. М.; 2021.</mixed-citation></citation-alternatives></ref></ref-list></back></article>
