biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Products10.30895/2221-996X-2020-20-1-21-29biopreparat-250Research ArticleОБЗОРЫREVIEWSИммунный ответ при иммунизации противовирусными вакцинамиImmune Response Induced by Immunisation with Antiviral Vaccineshttps://orcid.org/0000-0002-6807-508XАлпатоваН. А.AlpatovaN. A.

Алпатова Наталья Александровна, канд. биол. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Natalia А. Alpatova, Cand. Sci. (Biol.)

8/2 Petrovsky Blvd, Moscow 127051

alpatova@expmed.ruhttps://orcid.org/0000-0002-9377-1378АвдееваЖ. И.AvdeevaZh. I.

Авдеева Жанна Ильдаровна, д-р мед. наук, проф.

Петровский б-р, д. 8, стр. 2, Москва, 127051

Zhanna I. Avdeeva, Dr. Sci. (Med.), Professor

8/2 Petrovsky Blvd, Moscow 127051

avdeeva@expmed.ruhttps://orcid.org/0000-0002-6176-5934ГайдероваЛ. А.GayderovaL. A.

Гайдерова Лидия Александровна, канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Lidia A. Gayderova, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

gaiderova@expmed.ruhttps://orcid.org/0000-0001-7864-8972ЛысиковаС. Л.LysikovaS. L.

Лысикова Светлана Леонидовна, канд. мед. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Svetlana L. Lysikova, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

Lisikova@expmed.ruhttps://orcid.org/0000-0003-3937-5208МедуницынН. В.MedunitsynN. V.

Медуницын Николай Васильевич, д-р мед. наук, проф., академик РАН

Петровский б-р, д. 8, стр. 2, Москва, 127051

Nikolay V. Medunitsyn, Dr. Sci. (Med.), Professor, Academician of the RAS

8/2 Petrovsky Blvd, Moscow 127051

Medunitcin@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation2020170120202012129Copyright © Алпатова Н.А., Авдеева Ж.И., Гайдерова Л.А., Лысикова С.Л., Медуницын Н.В., 20202020Алпатова Н.А., Авдеева Ж.И., Гайдерова Л.А., Лысикова С.Л., Медуницын Н.В.Alpatova N.A., Avdeeva Z.I., Gayderova L.A., Lysikova S.L., Medunitsyn N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.biopreparations.ru/jour/article/view/250

Обзор посвящен вопросам, связанным с особенностями формирования поствакцинального иммунитета при использовании разных типов противовирусных вакцин, а также проблемам повышения иммуногенности вакцин и эффективности вакцинопрофилактики. Вакцины, содержащие высокоочищенные и рекомбинантные антигены, полученные с помощью современных технологий, характеризуются более низкой реактогенностью и более высоким профилем безопасности, но являются менее иммуногенными, по сравнению с живыми вакцинами. Для многих инфекционных вирусных заболеваний до настоящего времени эффективные вакцины не разработаны. Поиск путей усиления иммуногенных свойств вакцин для повышения эффективности вакцинации и разработка новых вакцинных препаратов, обеспечивающих надежную защиту организма от инфекции, является актуальным. Цель работы – провести анализ особенностей развития иммунного ответа на противовирусные вакцины и подходов к повышению их иммуногенности с помощью адъювантов. Рассмотрены типы противовирусных вакцин, а также особенности развития иммунного ответа в зависимости от природы специфического антигена. Обоснована целесообразность применения адъювантов для усиления и модуляции индуцированного иммунного ответа. Проанализированы механизмы, обуславливающие стимулирующий эффект адъювантов. Обобщены сведения об адъювантах, входящих в состав зарегистрированных вакцин для человека. Обозначена необходимость проведения дальнейших исследований в области повышения эффективности вакцинации, одним из направлений которых является использование в качестве адъювантов лекарственных препаратов на основе рекомбинантных цитокинов человека.

The review is devoted to specific aspects of the development of post-vaccination immunity following immunisation with different types of antiviral vaccines, as well as to ways of increasing immunogenicity of vaccines and effectiveness of preventive vaccination. Vaccines containing highly purified and recombinant antigens obtained using modern technologies have lower reactogenicity and a higher safety profile, but are less immunogenic compared to live vaccines. Effective vaccines have not been developed for many viral infections yet. Therefore, it is critical to search for ways to enhance immunogenic properties of vaccines in order to increase the efficiency of vaccination, and to develop new vaccine formulations that provide reliable protection of the body against infection. The aim of the paper was to analyse specific aspects of immune response development following immunisation with antiviral vaccines, and approaches to increasing their immunogenicity using adjuvants. It reviews different types of antiviral vaccines, as well as specific aspects of immune response development depending on the nature of a specific antigen. The paper substantiates the use of adjuvants to enhance and regulate the induced immune response. It analyses mechanisms that determine the stimulating effect of adjuvants and summarises data on the adjuvants used in the licensed vaccines for human use. The authors highlight the need for further research to increase the efficiency of vaccination and suggest that one of potential solutions is the use of adjuvants based on recombinant human cytokines.

вакцинывирусиммунитетадъювантантителаТ-клеткииммуногенность вакцинvaccinesvirusimmunityadjuvantantibodiesT cellsvaccine immunogenicityРабота выполнена в рамках государственного задания ФГБУ «НЦЭСМП» Минздрава России № 056-00003-20-00 на проведение прикладных научных исследований (номер государственного учета НИР AAAA-A18-118021590046-9)The study reported in this publication was carried out as part of a publicity funded research project No. 056-00003-20-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&D public accounting No. AAAA-A18-118021590046-9)ReferencesПетров РВ, Хаитов РМ. Иммуногены и вакцины нового поколения. М.: ГЭОТАР-Медиа; 2011.Petrov RV, Khaitov RM. Immunogens and vaccines of the new generation. Moscow: GEOTAR-Media; 2011 (In Russ.)Зверев ВВ, Юминова НВ. Вакцинопрофилактика вирусных инфекций от Э. Дженнера до настоящего времени. Вопросы вирусологии. 2012;(S1):33–42.Zverev VV, Yumi nova NV. Vaccines. Prevention of viral infections from E. Jenner to date. Voprosy virusologii = Problems of Virology. 2012;(S1):33–42 (In Russ.)Ярилин АА. Иммунология. М.: ГЭОТАР-Медиа; 2010.Yarilin AA. Immunology. Moscow: GEOTAR-Media; 2010 (In Russ.)Хаитов РМ, Пащенков МВ, Пинегин БВ. Роль паттернраспознающих рецепторов во врожденном и адаптивном иммунитете. Иммунология. 2009;30(1):66–76.Khaitov RM, Pashchenkov MV, Pinegin BV. The role of patternrecognizing receptors in congenital and active immunity in innate and adaptive immunity. Immunologiya = Immunology. 2009;30(1):66–76 (In Russ.)Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22(2):240–73. https://doi.org/10.1128/CMR.00046-08Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22(2):240–73. https://doi.org/10.1128/CMR.00046-08Хаитов РМ. Иммунология. М.: ГЭОТАР-Медиа; 2013.Khaitov RM. Immunology. Moscow: GEOTAR-Media; 2013 (In Russ.)Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11:373–84. http://doi.org/10.1038/ni.1863Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11:373–84. http://doi.org/10.1038/ni.1863Kumar H, Kawai T, Akira S. Pathogen recognition in the innate immune response. Biochem J. 2009;420(1):1–16. http://doi.org/10.1042/BJ20090272Kumar H, Kawai T, Akira S. Pathogen recognition in the innate immune response. Biochem J. 2009;420(1):1–16. http://doi.org/10.1042/BJ20090272Lipinska-Gediga M. Innate Response to Infection. J Clin Cell Immunol. 2013;S13:008. http://doi.org/10.4172/2155-9899.S13-008Lipinska-Gediga M. Innate Response to Infection. J Clin Cell Immunol. 2013;S13:008. http://doi.org/10.4172/2155-9899.S13-008Thompson MR, Kaminski JJ, Kurt-Jones EA, Fitzgerald КА. Pattern recognition receptors and the innate immune response to viral infection. Viruses. 2011;3(6):920–40. http://doi.org/10.3390/v3060920Thompson MR, Kaminski JJ, Kurt-Jones EA, Fitzgerald КА. Pattern recognition receptors and the innate immune response to viral infection. Viruses. 2011;3(6):920–40. http://doi.org/10.3390/v3060920Медуницын НВ, Миронов АН, Мовсесянц АА. Теория и практика вакцинологии. М.: Ремедиум; 2015.Medunitsyn NV, Mironov AN, Movsesyants AA. Theory and practice of vaccinology. Moscow: Remedium; 2015 (In Russ.)Skwarczynski M, Toth I. Peptide-based synthetic vaccines. Chem Sci. 2016;7(2):842–54. http://doi.org/10.1039/c5sc03892hSkwarczynski M, Toth I. Peptide-based synthetic vaccines. Chem Sci. 2016;7(2):842–54. http://doi.org/10.1039/c5sc03892hO E, Lee YT, Ko EJ, Kim KH, Lee YN, Song JM, et al. Roles of major histocompatibility complex class II in inducing protective immune responses to influenza vaccination. J Virol. 2014;88(14):7764–75. https://doi.org/10.1128/JVI.00748-14O E, Lee YT, Ko EJ, Kim KH, Lee YN, Song JM, et al. Roles of major histocompatibility complex class II in inducing protective immune responses to influenza vaccination. J Virol. 2014;88(14):7764–75. https://doi.org/10.1128/JVI.00748-14Plotkin SA. Correlates of vaccine-induced immunity. Clin Infect Dis. 2008;47(3):401–9. http://dx.doi.org/10.1086/589862Plotkin SA. Correlates of vaccine-induced immunity. Clin Infect Dis. 2008;47(3):401–9. http://dx.doi.org/10.1086/589862Zepp F. Principles of vaccination. Methods Mol Biol. 2016;1403:57–84 https://doi.org/10.1007/978-1-4939-33877_3Zepp F. Principles of vaccination. Methods Mol Biol. 2016;1403:57–84 https://doi.org/10.1007/978-1-4939-33877_3Orenstein WA, Seib K, Graham-Rowe D, Berkley S. Contemporary vaccine challenges: improving global health one shot at a time. Sci Transl Med. 2014;6(253):253ps11. https://doi.org/10.1126/scitranslmed.3009848Orenstein WA, Seib K, Graham-Rowe D, Berkley S. Contemporary vaccine challenges: improving global health one shot at a time. Sci Transl Med. 2014;6(253):253ps11. https://doi.org/10.1126/scitranslmed.3009848Plotkin SA. Correlates of protection induced by vaccination. Clin Vaccine Immunol. 2010;17(7):1055–65. https://doi.org/10.1128/CVI.00131-10Plotkin SA. Correlates of protection induced by vaccination. Clin Vaccine Immunol. 2010;17(7):1055–65. https://doi.org/10.1128/CVI.00131-10Griffiths KL, Khader SA. Novel vaccine approaches for protection against intracellular pathogens. Curr Opin Immunol. 2014;28:58–63. https://doi.org/10.1016/j.coi.2014.02.003Griffiths KL, Khader SA. Novel vaccine approaches for protection against intracellular pathogens. Curr Opin Immunol. 2014;28:58–63. https://doi.org/10.1016/j.coi.2014.02.003Querec T, Bennouna S, Alkan S, Laouar Y, Gorden K, Flavell R, et al. Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J Exp Med. 2006;203(2):413–24. https://doi.org/10.1084/jem.20051720Querec T, Bennouna S, Alkan S, Laouar Y, Gorden K, Flavell R, et al. Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J Exp Med. 2006;203(2):413–24. https://doi.org/10.1084/jem.20051720Querec TD, Akondy RS, Lee EK, Cao W, Nakaya HI, Teuwen D, et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol. 2009;10(1):116–25. https://doi.org/10.1038/ni.1688Querec TD, Akondy RS, Lee EK, Cao W, Nakaya HI, Teuwen D, et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol. 2009;10(1):116–25. https://doi.org/10.1038/ni.1688Poland JD, Calisher CH, Monath TP, Downs WG, Murphy K. Persistence of neutralizing antibody 30–35 years after immunization with 17D yellow fever vaccine. Bull World Health Organ. 1981;59(6):895–900.Poland JD, Calisher CH, Monath TP, Downs WG, Murphy K. Persistence of neutralizing antibody 30–35 years after immunization with 17D yellow fever vaccine. Bull World Health Organ. 1981;59(6):895–900.Koyama S, Ishii KJ, Kumar H, Tanimoto T, Coban C, Uematsu S, et al. Differential role of TLRand RLR-signaling in the immune responses to influenza A virus infection and vaccination. J Immunol. 2007;179(7):4711–20. https://doi.org/10.4049/jimmunol.179.7.4711Koyama S, Ishii KJ, Kumar H, Tanimoto T, Coban C, Uematsu S, et al. Differential role of TLRand RLR-signaling in the immune responses to influenza A virus infection and vaccination. J Immunol. 2007;179(7):4711–20. https://doi.org/10.4049/jimmunol.179.7.4711Vetter V, Denizer G, Friedland LR, Krishnan J, Shapiro M. Understanding modern-day vaccines: what you need to know. Ann Med. 2018;50(2):110–20. https://doi.org/10.1080/07853890.2017.1407035Vetter V, Denizer G, Friedland LR, Krishnan J, Shapiro M. Understanding modern-day vaccines: what you need to know. Ann Med. 2018;50(2):110–20. https://doi.org/10.1080/07853890.2017.1407035Bastola R, Noh G, Keum T, Bashyal S, Seo JE, Choi J, et al. Vaccine adjuvants: smart components to boost the immune system. Arch Pharm Res. 2017;40(11):1238–48. https://doi.org/10.1007/s12272-017-0969-zBastola R, Noh G, Keum T, Bashyal S, Seo JE, Choi J, et al. Vaccine adjuvants: smart components to boost the immune system. Arch Pharm Res. 2017;40(11):1238–48. https://doi.org/10.1007/s12272-017-0969-zCoffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity. 2010;33(4):492–503. https://doi.org/10.1016/j.immuni.2010.10.002Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity. 2010;33(4):492–503. https://doi.org/10.1016/j.immuni.2010.10.002Apostolico JS, Lunardelli VA, Coirada FC, Boscardin SB, Rosa DS. Adjuvants: classification, modus operandi, and licensing. J Immunol Res. 2016;2016:1459394. https://doi.org/10.1155/2016/1459394Apostolico JS, Lunardelli VA, Coirada FC, Boscardin SB, Rosa DS. Adjuvants: classification, modus operandi, and licensing. J Immunol Res. 2016;2016:1459394. https://doi.org/10.1155/2016/1459394Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011;12(6):509–17. https://doi.org/10.1038/ni.2039Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011;12(6):509–17. https://doi.org/10.1038/ni.2039Lee S, Nguyen MT. Recent advances of vaccine adjuvants for infectious diseases. Immune Netw. 2015;15(2):51–7. https://doi.org/10.4110/in.2015.15.2.51Lee S, Nguyen MT. Recent advances of vaccine adjuvants for infectious diseases. Immune Netw. 2015;15(2):51–7. https://doi.org/10.4110/in.2015.15.2.51Steinhagen F, Kinjo T, Bode C, Klinman DM. TLR-based immune adjuvants. Vaccine. 2011;29(17):3341–55. https://doi.org/10.1016/j.vaccine.2010.08.002Steinhagen F, Kinjo T, Bode C, Klinman DM. TLR-based immune adjuvants. Vaccine. 2011;29(17):3341–55. https://doi.org/10.1016/j.vaccine.2010.08.002Tukhvatulin AI, Dzharullaeva AS, Tukhvatulina NM, Shcheblyakov DV, Shmarov MM, Dolzhikova IV, et al. Powerful complex immunoadjuvant based on synergistic effect of combined TLR4 and NOD2 activation significantly enhances magnitude of humoral and cellular adaptive immune responses. PLoS One. 2016; 11(5):e0155650. https://doi.org/10.1371/journal.pone.0155650Tukhvatulin AI, Dzharullaeva AS, Tukhvatulina NM, Shcheblyakov DV, Shmarov MM, Dolzhikova IV, et al. Powerful complex immunoadjuvant based on synergistic effect of combined TLR4 and NOD2 activation significantly enhances magnitude of humoral and cellular adaptive immune responses. PLoS One. 2016; 11(5):e0155650. https://doi.org/10.1371/journal.pone.0155650Awate S, Babiuk LA, Mutwiri G. Mechanisms of action of adjuvants. Front Immunol. 2013;4:114. https://doi.org/10.3389/fimmu.2013.00114Awate S, Babiuk LA, Mutwiri G. Mechanisms of action of adjuvants. Front Immunol. 2013;4:114. https://doi.org/10.3389/fimmu.2013.00114Mosca F, Tritto E, Muzzi A, Monaci E, Bagnoli F, Iavarone C, et al. Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci USA. 2008;105(30):10501– 06. https://doi.org/10.1073/pnas.0804699105Mosca F, Tritto E, Muzzi A, Monaci E, Bagnoli F, Iavarone C, et al. Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci USA. 2008;105(30):10501– 06. https://doi.org/10.1073/pnas.0804699105Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nat Med. 2013;19(12):1597–608. https://doi.org/10.1038/nm.3409Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nat Med. 2013;19(12):1597–608. https://doi.org/10.1038/nm.3409Del Giudice G, Rappuoli R, Didierlaurent AM. Correlates of adjuvanticity: a review on adjuvants in licensed vaccines. Semin Immunol. 2018;39:14–21. https://doi.org/10.1016/j.smim.2018.05.001Del Giudice G, Rappuoli R, Didierlaurent AM. Correlates of adjuvanticity: a review on adjuvants in licensed vaccines. Semin Immunol. 2018;39:14–21. https://doi.org/10.1016/j.smim.2018.05.001Di Pasquale A, Preiss S, Tavares Da Silva F, Garcon N. Vaccine adjuvants: from 1920 to 2015 and beyond. Vaccines. 2015;3(2):320–43. https://doi.org/10.3390/vaccines3020320Di Pasquale A, Preiss S, Tavares Da Silva F, Garcon N. Vaccine adjuvants: from 1920 to 2015 and beyond. Vaccines. 2015;3(2):320–43. https://doi.org/10.3390/vaccines3020320Wagner R, Hildt E. Composition and mode of action of adjuvants in licensed viral vaccines. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2019;62(4):462– 71. https://doi.org/10.1007/s00103-019-02921-1Wagner R, Hildt E. Composition and mode of action of adjuvants in licensed viral vaccines. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2019;62(4):462– 71. https://doi.org/10.1007/s00103-019-02921-1Moyer TJ, Zmolek AC, Irvine DJ. Beyond antigens and adjuvants: formulating future vaccines. J Clin Invest. 2016;126(3):799–808. https://doi.org/10.1172/JCI81083Moyer TJ, Zmolek AC, Irvine DJ. Beyond antigens and adjuvants: formulating future vaccines. J Clin Invest. 2016;126(3):799–808. https://doi.org/10.1172/JCI81083Rambe DS, Giudice GD, Rossi S, Sanicas M. Safety and mechanism of action of licensed vaccine adjuvants. International Current Pharmaceutical Journal. 2015;4(8):420– 31. https://doi.org/10.3329/icpj.v4i8.24024Rambe DS, Giudice GD, Rossi S, Sanicas M. Safety and mechanism of action of licensed vaccine adjuvants. International Current Pharmaceutical Journal. 2015;4(8):420– 31. https://doi.org/10.3329/icpj.v4i8.24024Kazmin D, Nakaya HI, Lee EK, Johnson MJ, van der Most R, van den Berg RA, et al. Systems analysis of protective immune responses to RTS,S malaria vaccination in humans. Proc Natl Acad Sci USA. 2017;114(9):2425–30. https://doi.org/10.1073/pnas.1621489114Kazmin D, Nakaya HI, Lee EK, Johnson MJ, van der Most R, van den Berg RA, et al. Systems analysis of protective immune responses to RTS,S malaria vaccination in humans. Proc Natl Acad Sci USA. 2017;114(9):2425–30. https://doi.org/10.1073/pnas.1621489114Leroux-Roels G. Unmet needs in modern vaccinology: adjuvants to improve the immune response. Vaccine. 2010;28(Suppl 3):C25–36. https://doi.org/10.1016/j.vaccine.2010.07.021Leroux-Roels G. Unmet needs in modern vaccinology: adjuvants to improve the immune response. Vaccine. 2010;28(Suppl 3):C25–36. https://doi.org/10.1016/j.vaccine.2010.07.021Хантимирова ЛМ, Козлова ТЮ, Постнова ЕЛ, Шевцов ВА, Рукавишников АВ. Ретроспективный анализ заболеваемости вирусным гепатитом B населения Российской Федерации с 2013 по 2017 г. в аспекте вакцинопрофилактики. БИОпрепараты. Профилактика, диагностика, лечение. 2018;18(4):225–35. https://doi.org/10.30895/2221-996X-2018-18-4-225-235Khantimirova LM, Kozlova TYu, Postnova EL, Shevtsov VA, Rukavishnikov AV. Retrospective analysis of viral hepatitis B incidence in Russia from 2013 to 2017 in the context of preventive vaccination. BIOpreparaty. Profilaktika, diagnostika, lechenie = BIOpreparations. Prevention, Diagnosis, Treatment. 2018;18(4):225–35 (In Russ.) https://doi.org/10.30895/2221-996X-2018-18-4-225-235Laupeze B, Herve C, Di Pasquale A, Tavares Da Silva F. Adjuvant systems for vaccines: 13 years of post-licensure experience in diverse populations have progressed the way adjuvanted vaccine safety is investigated and understood. Vaccine. 2019;37(38):5670–80. https://doi.org/10.1016/j.vaccine.2019.07.098Laupeze B, Herve C, Di Pasquale A, Tavares Da Silva F. Adjuvant systems for vaccines: 13 years of post-licensure experience in diverse populations have progressed the way adjuvanted vaccine safety is investigated and understood. Vaccine. 2019;37(38):5670–80. https://doi.org/10.1016/j.vaccine.2019.07.098Nunberg JH, Doyle MV, York SM, York CJ. Interleukin 2 acts as an adjuvant to increase the potency of inactivated rabies virus vaccine. Proc Natl Acad Sci USA. 1989;86(11):4240–3. https://doi.org/10.1073/pnas.86.11.4240Nunberg JH, Doyle MV, York SM, York CJ. Interleukin 2 acts as an adjuvant to increase the potency of inactivated rabies virus vaccine. Proc Natl Acad Sci USA. 1989;86(11):4240–3. https://doi.org/10.1073/pnas.86.11.4240Ben-Sasson SZ, Caucheteux S, Crank M, Hu-Li J, Paul WE. IL-1 acts on T cells to enhance the magnitude of in vivo immune responses. Cytokine. 2011;56(1):122–5. https://doi.org/10.1016/j.cyto.2011.07.006Ben-Sasson SZ, Caucheteux S, Crank M, Hu-Li J, Paul WE. IL-1 acts on T cells to enhance the magnitude of in vivo immune responses. Cytokine. 2011;56(1):122–5. https://doi.org/10.1016/j.cyto.2011.07.006Li Y, Zhou M, Luo Z, Zhang Y, Cui M, Chen H, et al. Overexpression of interleukin-7 extends the humoral immune response induced by rabies vaccination. J Virol. 2017;91(7):e02324-16. https://doi.org/10.1128/JVI.02324-16Li Y, Zhou M, Luo Z, Zhang Y, Cui M, Chen H, et al. Overexpression of interleukin-7 extends the humoral immune response induced by rabies vaccination. J Virol. 2017;91(7):e02324-16. https://doi.org/10.1128/JVI.02324-16Gai W, Zheng W, Wang C, Wong G, Song Y, Zheng X. Immunization with recombinant rabies virus expressing Interleukin-18 exhibits enhanced immunogenicity and protection in mice. Oncotarget. 2017;8(53):91505–15. https://doi.org/10.18632/oncotarget.21065Gai W, Zheng W, Wang C, Wong G, Song Y, Zheng X. Immunization with recombinant rabies virus expressing Interleukin-18 exhibits enhanced immunogenicity and protection in mice. Oncotarget. 2017;8(53):91505–15. https://doi.org/10.18632/oncotarget.21065Ju B, Li D, Ji X, Liu J, Peng H, Wang S, et al. Interleukin-21 administration leads to enhanced antigen-specific T cell responses and natural killer cells in HIV-1 vaccinated mice. Cell Immunol. 2016;303:55–65. https://doi.org/10.1016/j.cellimm.2016.03.006Ju B, Li D, Ji X, Liu J, Peng H, Wang S, et al. Interleukin-21 administration leads to enhanced antigen-specific T cell responses and natural killer cells in HIV-1 vaccinated mice. Cell Immunol. 2016;303:55–65. https://doi.org/10.1016/j.cellimm.2016.03.006Grasse M, Meryk A, Miggitsch C, Grubeck-Loebenstein B. GM-CSF improves the immune response to the diphtheriacomponent in a multivalent vaccine. Vaccine. 2018;36(31):4672– 80. https://doi.org/10.1016/j.vaccine.2018.06.033Grasse M, Meryk A, Miggitsch C, Grubeck-Loebenstein B. GM-CSF improves the immune response to the diphtheriacomponent in a multivalent vaccine. Vaccine. 2018;36(31):4672– 80. https://doi.org/10.1016/j.vaccine.2018.06.033Toporovski R, Morrow MP, Weiner DB. Interferons as potential adjuvants in prophylactic vaccines. Expert Opin Biol Ther. 2010;10(10):1489–500. https://doi.org/10.1517/14712598.2010.521495Toporovski R, Morrow MP, Weiner DB. Interferons as potential adjuvants in prophylactic vaccines. Expert Opin Biol Ther. 2010;10(10):1489–500. https://doi.org/10.1517/14712598.2010.521495Симбирцев АС, Петров АВ, Пигарева НВ, Николаев АТ. Новые возможности применения рекомбинантных цитокинов в качестве адъювантов при вакцинации. БИОпрепараты. Профилактика, диагностика, лечение. 2011;(1):16–20.Simbirtsev AS, Petrov AV, Pigareva NV, Nikolaev AT. New opportunities for using recombinant cytokines as adjuvants for vaccination. BIOpreparaty. Profilaktika, diagnostika, lechenie = BIOpreparations. Prevention, Diagnosis, Treatment. 2011;(1):16–20 (In Russ.)Miquilena-Colina ME, Lozano-Rodriguez T, Garcia-Pozo L, Saez A, Rizza P, Capone I, et al. Recombinant interferonα2b improves immune response to hepatitis B vaccination in haemodialysis patients: results of a randomised clinical trial. Vaccine. 2009;27(41):5654–60. https://doi.org/10.1016/j.vaccine.2009.07.014Miquilena-Colina ME, Lozano-Rodriguez T, Garcia-Pozo L, Saez A, Rizza P, Capone I, et al. Recombinant interferonα2b improves immune response to hepatitis B vaccination in haemodialysis patients: results of a randomised clinical trial. Vaccine. 2009;27(41):5654–60. https://doi.org/10.1016/j.vaccine.2009.07.014Yağci M, Acar K, Sucak GT, Yamac K, Haznedar R. Hepatitis B virus vaccine in lymphoproliferative disorders: a prospective randomized study evaluating the efficacy of granulocyte-macrophage colony stimulating factor as a vaccine adjuvant. Eur J Haematol. 2007;79(4):292–6. https://doi.org/10.1111/j.1600-0609.2007.00912.xYağci M, Acar K, Sucak GT, Yamac K, Haznedar R. Hepatitis B virus vaccine in lymphoproliferative disorders: a prospective randomized study evaluating the efficacy of granulocyte-macrophage colony stimulating factor as a vaccine adjuvant. Eur J Haematol. 2007;79(4):292–6. https://doi.org/10.1111/j.1600-0609.2007.00912.x

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