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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">epidemiology</journal-id><journal-title-group><journal-title xml:lang="ru">Эпидемиология и Вакцинопрофилактика</journal-title><trans-title-group xml:lang="en"><trans-title>Epidemiology and Vaccinal Prevention</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2073-3046</issn><issn pub-type="epub">2619-0494</issn><publisher><publisher-name>«Numicom» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.31631/2073-3046-2023-22-6-183-200</article-id><article-id custom-type="elpub" pub-id-type="custom">epidemiology-1919</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>ОБЗОР</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEW</subject></subj-group></article-categories><title-group><article-title>Проблемы и коллизии вакцинологии</article-title><trans-title-group xml:lang="en"><trans-title>Problems and Collisions of Vaccinology</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Харченко</surname><given-names>Е. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Kharchenko</surname><given-names>E. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Евгений Петрович Харченко – д. б. н., ведущий научный сотрудник</p><p>+7 (904) 338-22-80</p><p>194223, Россия, Санкт-Петербург, пр. Тореза, 44</p></bio><bio xml:lang="en"><p>Eugene P. Kharchenko – Dr. Sci. (Biol.), leader researcher</p><p>+7 (904) 338-22-80,</p><p>194223, Russian Federation, St. Petersburg, Toreza pr., 44</p></bio><email xlink:type="simple">neuro.children@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУН «Институт эволюционной физиологии и биохимии им. И. М. Сеченова» РАН</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Sechenov Institute of Evolutionary Physiology and Biochemistry</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>06</day><month>01</month><year>2024</year></pub-date><volume>22</volume><issue>6</issue><fpage>183</fpage><lpage>200</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Харченко Е.П., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Харченко Е.П.</copyright-holder><copyright-holder xml:lang="en">Kharchenko E.P.</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.epidemvac.ru/jour/article/view/1919">https://www.epidemvac.ru/jour/article/view/1919</self-uri><abstract><p>В статье рассматриваются ограниченность защитного потенциала иммунной системы, определяемая особенностями эволюционных механизмов, приведших к разнообразию белков, и эволюционно поздним возникновением адаптивной иммунной системы, а также проблемы, связанные с формированием иммунитета к вирусным инфекциям и иммунными коллизиями при вакцинации. На примере гемагглютинина вируса гриппа H1N1 и S-белка коронавируса SARS-Cov-2 иллюстрируются особенности аминокислотного состава их иммунодоминантных (НА1 и S1) и субдоминантных (НА2 и S2) субъединиц и анализируется возможность создания универсальной вакцины против гриппа. Излагается принцип нового метода выявления линейных пептидных иммуноэпитопов, распознаваемых МНС I и II, и биомаркеров долговременного иммунитета в поверхностных вирусных белках, используемых в вакцинах. Расссматриваются: модель протеолиза белков вакцин в иммунопротесомах и лизосомах; особенности аминокислотного состава поверхностных белков вирусов; вакцины, способные вызывать долговременный иммунитет; вирусы, вакцины к которым еще не разработаны, а также возможные коллизии с мРНК-вакцинами в связи с выявлением ограничений в кодировании генов.</p></abstract><trans-abstract xml:lang="en"><p>The article discusses the limitations of the protective potential of the immune system associated with the peculiarities of the evolutionary mechanisms of the emergence of protein diversity and the late emergence in the evolution of the adaptive immune system, as well as problems associated with the formation of immunity to viral infections and immune collisions during vaccination. Using the example of hemagglutinin of the H1N1 influenza virus and S protein of the SARS-Cov-2 coronavirus, the features of the amino acid composition of their immunodominant (NA1 and S1) and subdominant (NA2 and S2) subunits are illustrated and the possibility of creating a universal vaccine against influenza viruses is analyzed. The principle of a new method for detecting linear peptide immunoepitopes recognized by MHC I and II and biomarkers of long-term immunity in surface viral proteins used as vaccines is described. The model of proteolysis of vaccine proteins in immunoprotesomes and lysosomes, features of the amino acid composition of surface proteins of viruses to which vaccines cause long-term immunity, and viruses to which vaccines have not yet been developed, as well as possible collisions with mRNA vaccines are examined. Possible collisions with mRNA vaccines are also being considered in connection with the identification of gene encoding limitations.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>вакцины</kwd><kwd>вирусы</kwd><kwd>иммунодоминантность</kwd><kwd>иммуноэпитопы</kwd><kwd>иммунитет</kwd><kwd>прогнозирование</kwd><kwd>иммунные коллизии</kwd></kwd-group><kwd-group xml:lang="en"><kwd>vaccines</kwd><kwd>influenza viruses</kwd><kwd>immunodominance</kwd><kwd>immunoepitopes</kwd><kwd>immunity</kwd><kwd>prediction</kwd><kwd>immune collisions</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Nabel G.J., Fauci A.S. Induction of unnatural immunity: prospects for a broadly protective universal influenza vaccine. Nature Medicine. 2010;16(12):1389–1291. doi: 10.1038/nm1210-1389.</mixed-citation><mixed-citation xml:lang="en">Nabel G.J., Fauci A.S. Induction of unnatural immunity: prospects for a broadly protective universal influenza vaccine. Nature Medicine. 2010;16(12):1389–1291. doi: 10.1038/nm1210-1389.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Van Regenmortel M. An outdated notion of antibody specificity is one of the major detrimental assumptions of the structure-based reverse vaccinology paradigm, which prevented it from helping to develop an effective HIV-1 vaccine. Frontiers in Immunology, 2014, Vol. 5, pp. 1 –8. doi: 10.3389/fimmu.2014.00593.</mixed-citation><mixed-citation xml:lang="en">Van Regenmortel M. An outdated notion of antibody specificity is one of the major detrimental assumptions of the structure-based reverse vaccinology paradigm, which prevented it from helping to develop an effective HIV-1 vaccine. Frontiers in Immunology. 2014;5:1–8. doi: 10.3389/fimmu.2014.00593.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Van Regenmortel M.H.V. Specificity, polyspecificity and heterospecificity of antibody-antigen recognition. J. Mol. Recognit., 2014, Vol. 27, pp. 627-639. doi: 10.1002/jmr.2394.</mixed-citation><mixed-citation xml:lang="en">Van Regenmortel M.H.V. Specificity, polyspecificity and heterospecificity of antibody-antigen recognition. J. Mol. Recognit. 2014;27:627–639. doi: 10.1002/jmr.2394.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Victora GD, Nussenzweig MC. Germinal Centers. Annu. Rev. Immunol. 2022. 40:413–42. https://doi:10.1146/annurev-immunol-120419-022408</mixed-citation><mixed-citation xml:lang="en">Victora GD, Nussenzweig MC. Germinal Centers. Annu. Rev. Immunol. 2022; 40:413–42. https://doi:10.1146/annurev-immunol-120419-022408</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Young C, Brink R. The unique biology of germinal center B cells Immunity 2021 ; Vol. 54, pp. 1652-1664 . doi: 10.1016/j.immuni.2021.07.015 .</mixed-citation><mixed-citation xml:lang="en">Young C, Brink R. The unique biology of germinal center B cells Immunity. 2021;54:1652–1664. doi: 10.1016/j.immuni.2021.07.015.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Харченко Е. П. Иммуноэпитопный континуум родства белков и полиреактивность и аутореактивность антител. Медицинская иммунология. 2015. Т. 17, N. 4. C. 335–346. 10.15789/1563-0625-2015-4-335-346.</mixed-citation><mixed-citation xml:lang="en">Kharchenko E.P. Immune epitope continuum of the protein relationships, poly- and autoreactivity of antibodies, Medical Immunology /Meditsinskaya Immunologiya. 2015;17(4):335–346 (In Russ.). doi: 10.15789/1563-0625-2015-4-335-346</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Харченко Е. П. Распространенность генетической рекомбинации между вирусами и человеком, возможное ее влияние на вакцинацию. Эпидемиология и Вакцинопрофилактика. 2019;18(5):4–14. https://doi: 10.31631/2073-3046-2019-18-6-4-14.</mixed-citation><mixed-citation xml:lang="en">Kharchenko EP. The Occurrence of Genetic Recombination between Viruses and Human – its Possible Influence on Vaccination. Epidemiology and Vaccinal Prevention. 2019;18(5):4–14 (In Russ.). doi: 10.31631/2073-3046-2019-18-6-4-14.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Харченко Е. П. Распространенность в геноме вирусов человека малых гомологичных и комплементарных фрагментов и возможная их роль. Инфекция и иммунитет. 2017. Т. 7, № 4. С. 393–404. doi: 10.15789/2220-7619-2017-4-393-404.</mixed-citation><mixed-citation xml:lang="en">Kharchenko E.P. Occurrence of small homologous and complementary fragments in human virus genomes and their possible role. Russian Journal of Infection and Immunity = Infektsiya i immunitet, 2017;7(4):393–404 (In Russ.). doi: 10.15789/2220-7619-2017-4-393-404</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Харченко Е. П. Коронавирус SARS-Cov-2: особенности структурных белков, контагиозность и возможные иммунные коллизии. Эпидемиология и Вакцинопрофилактика. 2020;19(2):13–30. https://doi: 10.31631/2073-3046-2020-19-2-13-30</mixed-citation><mixed-citation xml:lang="en">Kharchenko EP. The Coronavirus SARS-Cov-2: the Characteristics of Structural Proteins, Contagiousness, and Possible Immune Collisions. Epidemiology and Vaccinal Prevention. 2020;19(2):13–30 (In Russ.). https://doi: 10.31631/2073-3046-2020-19-2-13-30.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Dotan A, Muller S, Kanduc D, et al. The SARS-CoV-2 as an instrumental trigger of autoimmunity. Autoimmun Rev. 2021;20(4):102792. doi: 10.1016/j.autrev.2021.102792.</mixed-citation><mixed-citation xml:lang="en">Dotan A, Muller S, Kanduc D, et al. The SARS-CoV-2 as an instrumental trigger of autoimmunity. Autoimmun Rev. 2021;20(4):102792. doi: 10.1016/j.autrev.2021.102792.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Pradeu T., Carosella E.D. On the definition of a criterion of immunogenicity. Proc. Natl. Acad. Sci. USA, 2006, Vol. 103, pp. 17858-17863. 10.1073/pnas.0608683103</mixed-citation><mixed-citation xml:lang="en">Pradeu T., Carosella E.D. On the definition of a criterion of immunogenicity. Proc. Natl. Acad. Sci. USA, 2006;103:17858–17863. doi:10.1073/pnas.0608683103</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Кудряева А.А., Белогуров А.А. Протеасома: наномашинерия созидательного Успехи биологической химии, т. 59, 2019, с. 323–392.</mixed-citation><mixed-citation xml:lang="en">Kudriaeva AA., Belogurov AA. Proteasome: nanomachineery of the creative Progress of biological chemistry. 2019;59:323–392 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Altman M.O., Angeletti D., Yewdell J.W. Antibody Immunodominance: The Key to Understanding Influenza Virus Antigenic Drift. Viral Immunology. 2018. Vol. 31 , no 2, pp. 1–8 . doi: 10.1089/vim.2017.0129.</mixed-citation><mixed-citation xml:lang="en">Altman M.O., Angeletti D., Yewdell J. W. Antibody Immunodominance: The Key to Understanding Influenza Virus Antigenic Drift. Viral Immunology. 2018;31(2):1–8. doi: 10.1089/vim.2017.0129.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Ke Z., Oton J., Qu K., Cortese M., et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature. 2020. doi:10.1038/s41586-020-2665-2</mixed-citation><mixed-citation xml:lang="en">Ke Z., Oton J., Qu K., Cortese M., et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature. 2020. doi:10.1038/s41586-020-2665-2</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Akkaya M., Kwak K., Pierce S.K. B cell memory: building two walls of protection against pathogens. Nat Rev Immunol. 2020; vol. 20(4) pp. 229-238. doi::10.1038/s41577-019-0244-2.</mixed-citation><mixed-citation xml:lang="en">Akkaya M ., Kwak K ., Pierce S .K. B cell memory: building two walls of protection against pathogens. Nat Rev Immunol. 2020;20(4):229–238. doi::10.1038/s41577-019-0244-2.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Inoue T., Shinnakasu R., Kurosaki T. Generation of high quality memory B cells. Front Immunol. 2022; vol. 12: (825813). doi: 10.3389/fimmu.2021.825813.</mixed-citation><mixed-citation xml:lang="en">Inoue T., Shinnakasu R., Kurosaki T. Generation of high quality memory B cells. Front Immunol. 2022;12:(825813). doi: 10.3389/fimmu.2021.825813.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Narayanan H.V., Hoffmann A. From Antibody Repertoires to Cell-Cell Interactions to molecular networks: bridging scales in the germinal center. Front. Immunol 2022; vol. 13: (898078). doi: 10.3389/fimmu.2022. 898078.</mixed-citation><mixed-citation xml:lang="en">Narayanan H.V., Hoffmann A. From Antibody Repertoires to Cell-Cell Interactions to molecular networks: bridging scales in the germinal center. Front. Immunol. 2022;13:(898078). doi: 10.3389/fimmu.2022. 898078.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang H., Weyand C.M., Goronzy J. Hallmarks of the aging T-cell system. The FEBS Journal 2021; vol. 288 pp. 7123–7142 doi:10.1111/febs.15770 .</mixed-citation><mixed-citation xml:lang="en">Zhang H., Weyand C. M., Goronzy J. Hallmarks of the aging T-cell system. The FEBS Journal. 2021;288:7123–7142 doi:10.1111/febs.15770 .</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Peters B, Nielsen M, Sette A. T Cell Epitope Predictions. Annu. Rev. Immunol. 2020. vol. 38 pp. 123–45. doi: 10.1146/annurev-immunol-082119-124838</mixed-citation><mixed-citation xml:lang="en">Peters B, Nielsen M, Sette A. T Cell Epitope Predictions. Annu. Rev. Immunol. 2020;38:123–45. doi: 10.1146/annurev-immunol-082119-124838</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Loan Ping Eng, Tin Wee Tan, Joo Chuan Tong, Söllner J. Building MHC Class II Epitope Predictor Using Machine Learning Approaches. In: Peng Zhou and Jian Huang (eds.), Computational Peptidology, Methods in Molecular Biology. 2015. vol. 1268, doi: 10.1007/978-1-4939-2285-7_4,</mixed-citation><mixed-citation xml:lang="en">Loan Ping Eng, Tin Wee Tan, Joo Chuan Tong, Söllner J. Building MHC Class II Epitope Predictor Using Machine Learning Approaches. In: Peng Zhou and Jian Huang (eds.), Computational Peptidology, Methods in Molecular Biology, 2015;1268. doi: 10.1007/978-1-4939-2285-7_4,</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Söllner J. Computational Peptide Vaccinology. In: Peng Zhou and Jian Huang (eds.), Computational Peptidology, Methods in Molecular Biology. 2015. Vol. 1268, doi: 10.1007/978-1-4939-2285-7_13</mixed-citation><mixed-citation xml:lang="en">Söllner J. Computational Peptide Vaccinology. In: Peng Zhou and Jian Huang (eds.), Computational Peptidology, Methods in Molecular Biology. 2015;1268, doi: 10.1007/978-1-4939-2285-7_13.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Joglekar AV, Li G. T cell antigen discovery. Nature Methods. 2020. Vol. 18(8): pp. 873-880. 18(8):873-880.873-880. doi: 10.1038/s41592-020-0867-z</mixed-citation><mixed-citation xml:lang="en">Joglekar AV, Li G. T cell antigen discovery. Nature Methods. 2020;18(8):873 –880. doi: 10.1038/s41592-020-0867-z</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Харченко Е. П. Новый метод распознавания иммуноэпитопов, маркеры долговременного иммунитета, иммуносупрессивные домены и вакцины против COVID-19. Эпидемиология и Вакцинопрофилактика. 2022;21(1):4–20. https://doi:10.31631/2073-3046-2022-21-1-4-20.</mixed-citation><mixed-citation xml:lang="en">Kharchenko EP. Novel Method of Immunoepitope Recognition, Long-Term Immunity Markers, Immunosuppressive Domens and Vaccines against COVID-19. Epidemiology and Vaccinal Prevention. 2022;21(1):4–20 (In Russ.). doi: 10.31631/2073-3046-2022-21-1-4-20.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Briney B., Inderbitzin A., Joyce C.. Burton D.R. Commonality despite exceptional diversity in the baseline human antibody repertoire. NATURE. 2019. vol. 566(7744) pp. 393–397/doi.org/10.1038/s41586-019-0879-y .</mixed-citation><mixed-citation xml:lang="en">Briney B., Inderbitzin A., Joyce C., Burton D.R. Commonality despite exceptional diversity in the baseline human antibody repertoire. Nature. 2019;566(7744):393 – 397. doi:10.1038/s41586-019-0879-y.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Soto C., Bombardi R.G., Branchizio A., Kose N, et al. High frequency of shared clonotypes in human B cell receptor repertoires. Nature.2019. vol. 566(7744) pp. 398–402. doi. org/10.1038/s41586-019-0934-8</mixed-citation><mixed-citation xml:lang="en">Soto C., Bombardi R.G., Branchizio A., Kose N, et al. High frequency of shared clonotypes in human B cell receptor repertoires. Nature. 2019;566(7744):398 – 402. doi:10.1038/s41586-019-0934-8.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Харченко Е. П. Оптимизация прогнозирования вакцинных штаммов гриппа Эпидемиология и Вакцинопрофилактика. 2019;18(1):4–17. https://doi:10.31631/2073-3046-2019-18-1-4-17</mixed-citation><mixed-citation xml:lang="en">Kharchenko E. P. Optimization of the Predicting of the Influenza Vaccine Strains Epidemiology and Vaccinal Prevention. 2019;18(1):4 –17 (In Russ.). doi: 10.31631/2073-3046-2019-18-1-4-17.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Харченко Е. П. Поиски универсальной противогриппозной вакцины: возможности и ограничения. Эпидемиология и Вакцинопрофилактика. 2019;18(5):70–84. https://doi: 10.31631/2073-3046-2019-18-5-70-84.</mixed-citation><mixed-citation xml:lang="en">Kharchenko EP. The Search for a Universal Influenza Vaccine: Possibilities and Limitations. Epidemiology and Vaccinal Prevention. 2019;18(5):70–84 (In Russ.). doi: 10.31631/2073-3046-2019-18-5-70-84.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Gilesa BM., Ross TM. A computationally optimized broadly reactive antigen (COBRA) based H5N1 VLP vaccine elicits broadly reactive antibodies in mice and ferrets. Vaccine. Vol. 29, P. 3043–3054. doi:10.1016/j.vaccine.2011.01.100.</mixed-citation><mixed-citation xml:lang="en">Gilesa BM., Ross TM. A computationally optimized broadly reactive antigen (COBRA) based H5N1 VLP vaccine elicits broadly reactive antibodies in mice and ferrets. Vaccine. 2011;29:3043–3054. doi:10.1016/j.vaccine.2011.01.100.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Харченко Е. П. Три уровня прогнозирования штаммов вируса гриппа. Эпидемиология и Вакцинопрофилактика. 2019;18(2):4–17. https://doi: 10.31631/2073-3046-2019-18-2-4–17.</mixed-citation><mixed-citation xml:lang="en">Kharchenko E. P. Three Levels of the Predicting of the Influenza Vaccine Strains. Epidemiology and Vaccinal Prevention. 2019;18(2):4–17 (In Russ.). doi: 10.31631/2073-3046-2019-18-2-4–17.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Douglass J, Civelli O, Herbert E. Polyprotein gene expression: generation of diversity of neuroendocrine peptides. Annu Rev Biochem. 1984; Vol. 53. pp. 665–715. doi: 10.1146/annurev.bi.53.070184.003313.</mixed-citation><mixed-citation xml:lang="en">Douglass J, Civelli O, Herbert E. Polyprotein gene expression: generation of diversity of neuroendocrine peptides. Annu Rev Biochem. 1984;53:665 –715. doi: 10.1146/annurev.bi.53.070184.003313.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Ашмарин И. П., Фрейдлин И. С. Гипотеза об антителах как новейших регуляторах физиологических функций, созданных эволюцией. Журнал эволюционной биохимии и физиологии, 1989. Т. 25, № 2. С. 176–181.</mixed-citation><mixed-citation xml:lang="en">Ashmarin I.P., Freidlin I.S. Hypothesis on antibodies as the latest regulators of physiological functions created by evolution. Zhurnal evolyutsionnoy biokhimii i fiziologii = Journal of Evolutionary Biochemistry and Physiology, 1989;25(2):176 –181 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Murphy W.J., Longo D.L., A Possible Role for Anti-idiotype Antibodies in SARS-CoV-2 Infection and Vaccination. N Engl J Med 2022 Vol. 386. no 4, pp. 394–396. doi: 10.1056/NEJMcibr2113694.</mixed-citation><mixed-citation xml:lang="en">Murphy W.J., Longo D.L. A Possible Role for Anti-idiotype Antibodies in SARS-CoV-2 Infection and Vaccination. N Engl J Med. 2022;386(4):394 –396. doi: 10.1056/NEJMcibr2113694.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Naveed A., Naz D., Rahman S.U. Idiotype/anti-idiotype antibodies: as a glorious savior in COVID-19 pandemics. Translational Medicine Communications. 2021. Vol. 6. doi:10.1186/s41231-021-00097-y.</mixed-citation><mixed-citation xml:lang="en">Naveed A., Naz D., Rahman S. U. Idiotype/anti-idiotype antibodies: as a glorious savior in COVID-19 pandemics. Translational Medicine Communications. 2021;6. doi:10.1186/s41231-021-00097-y.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Dolgin E. Why rings of RNA could be the next blockbuster drug. 2023 . Nature . Vol. 622, pp. 22–24. doi:10.1038/d41586-023-03058-7.</mixed-citation><mixed-citation xml:lang="en">Dolgin E. Why rings of RNA could be the next blockbuster drug. Nature. 2023;622:22–24. doi:10.1038/d41586-023-03058-7 .</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Martínez MA, Jordan-Paiz A, Franco S, Nevot M. Synonymous Virus Genome Recoding as a Tool to Impact Viral Fitness. Trends Microbiol. 2016. Vol. 24. no 2. pp. 134–147. doi: 10.1016/j.tim.2015.11.002.</mixed-citation><mixed-citation xml:lang="en">Martínez MA, Jordan-Paiz A, Franco S, Nevot M. Synonymous Virus Genome Recoding as a Tool to Impact Viral Fitness. Trends Microbiol. 2016;24(2):134 –147. doi: 10.1016/j.tim.2015.11.002.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
