References

epidemiology

Эпидемиология и Вакцинопрофилактика

Epidemiology and Vaccinal Prevention

2073-30462619-0494

«Numicom» LLC

10.31631/2073-3046-2018-17-1-76-86

epidemiology-412

Research Article

ОБЗОРНАЯ СТАТЬЯ

Перспективы использования агонистов рецепторов врожденного иммунитета и дефектных вирусных интерферирующих частиц в качестве адъювантов нового поколения

Agonists of Receptors of the Innate Immunity and Defective Viral Particles as New Generation of Adjuvants

Свитич

О. А.

Svitich

O. A.

svitichoa@yandex.ru

Лавров

В. Ф.

Lavrov

V. F.

Кукина

П. И.

Kukina

P. I.

Скандарян

А. А.

Iskandaryan

A. A.

Ганковская

Л. В.

Gankovskaya

L. V.

Зверев

В. В.

Zverev

V. V.

ФГБНУ «НИИ вакцин и сывороток им. И. И. Мечникова»; ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет); ФГБОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияI. I. Mechnikov Scientific Research Institute of Vaccines and Sera of the Ministry of Healthcare of the Russian Federation Moscow; Sechenov University, of the Ministry of Healthcare of the Russian Federation Moscow; Russian National Research Medical University, of the Ministry of Healthcare of the Russian FederationRussian Federation

ФГБНУ «НИИ вакцин и сывороток им. И. И. Мечникова»; ФГБОУ ДПО «РМАНПО» Минздрава РоссииРоссияI. I. Mechnikov Scientific Research Institute of Vaccines and Sera of the Ministry of Healthcare of the Russian Federation Moscow; Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of the Russian FederationRussian Federation

ФГБНУ «НИИ вакцин и сывороток им. И. И. Мечникова»; ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)РоссияI. I. Mechnikov Scientific Research Institute of Vaccines and Sera of the Ministry of Healthcare of the Russian Federation Moscow; Sechenov University, of the Ministry of Healthcare of the Russian Federation MoscowRussian Federation

ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)РоссияSechenov University, of the Ministry of Healthcare of the Russian Federation MoscowRussian Federation

ФГБОУ ВО РНИМУ им. Н.И. Пирогова Минздрава РоссииРоссияRussian National Research Medical University, of the Ministry of Healthcare of the Russian FederationRussian Federation

2018

20022018

1717686

2018

Свитич О.А., Лавров В.Ф., Кукина П.И., Скандарян А.А., Ганковская Л.В., Зверев В.В.

Svitich O.A., Lavrov V.F., Kukina P.I., Iskandaryan A.A., Gankovskaya L.V., Zverev V.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.epidemvac.ru/jour/article/view/412

Вакцины в течение многих лет выступают в качестве одних из наиболее эффективных и успешно применяемых медицинских препаратов. Добавление в состав вакцин адъювантов, как правило, существенно усиливает иммунный ответ на их введение. Установлено, что формирование поствакцинального иммунитета начинается сразу после введения вакцины путём активации факторов врожденного иммунитета при взаимодействии патоген-ассоциированных молекулярных образов в составе вакцин, с патоген-распознающими рецепторами (PRR) иммунокомпетентных клеток реципиента. Показано также, что активаторы PRR, в том числе, агонисты ТOLL-подобных рецепторов (TLRs) и полинуклеотидные олигомеры инозиновой и цитидиловой кислот обладают способностью существенно увеличивать иммуногенность вакцин, в связи с чем предпринимаются попытки их использования при создании новых типов адъювантов. Дефектные интерферирующие вирусные частицы относят к группе эффективных стимуляторов врождённого иммунитета и они также могут рассматриваться в качестве перспективных вакцинных адъювантов.

Vaccines for many years act as one of the most effective and successfully used medicines. Vaccines obtained by traditional methods contain in their composition live, weakened or killed microorganisms (bacteria, viruses, etc.). Now more often, modern, split, subunit, recombinant, polyvalent and some other types of vaccines are being used. The addition of adjuvants to vaccines generally increases the immune response to their administration. It was established that the formation of postvaccinal immunity begins immediately after the introduction of the vaccine, by activating the factors of innate immunity in the interaction of pathogen-associated molecular patterns (PAMPs), in vaccines, with the pathogen-recognition receptors (PRRs) of the immunocompetent cells of the recipient. It is also shown that PRRs activators, including TOLL-like receptor agonists (TLRs) and poly (I:C) polynucleotide oligomers of inosine and cytidylic acids, have the ability to substantially increase the immunogenicity of vaccines, and attempts are being made to use them creation of new types of adjuvants. Defective interfering viral particles (D-particles, DIPs) are also classed as effective stimulants of innate immunity and can also be considered promising vaccine adjuvants.

иммунитетвакцинацияадъювантыVZVRAG1RAG2ди-частицыPRRTLRPAMPИФН

immunityvaccinationadjuvantsVZVRAG1RAG2DIPPRRTLRPAMPIFN

References1

Ribeiro C. M., Schijns V. E. Immunology of vaccine adjuvants. Methods Mol. Biol. 2010; 626: 1–14.

Eibl M. M., Wolf H. M. Vaccination in patients with primary immune deficiency, secondary immune deficiency and autoimmunity with immune regulatory abnormalities. Immunotherapy 2015; 7: 1273–1292.

Eibl M. M., Wolf H. M. Vaccination in patients with primary immune deficiency, secondary immune deficiency and autoimmunity with immune regulatory abnormalities. Immunotherapy. 2015; 7: 1273–1292.

Glenny A. T., Barr M. The precipitation of diphtheria toxoid by potash alum. J. Pathol. Bacteriol. 1931; 34: 131–138.

Tong N. K. C., Beran J., Kee S. A., Miguel J. L., Sánchez C., Bayas J. M. et al. Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients. Kidney Int. 2005; 68: 2298–2303.

Baz M., Luke C. J., Cheng X., Jin H., Subbarao K. H5N1 vaccines in humans. Virus Res. 2013; 178: 78–98.

Stephenson I., Nicholson K. G., Colegate A., Podda A., Wood J., Ypma E., Zambon M. Boosting immunity to influenza H5N1 with MF59-adjuvanted H5N3 A/Duck/ Singapore/97 vaccine in a primed human population. Vaccine 2003; 21: 1687–1693.

Лабжинов П. А., Свитич О. А., Ганковская Л. В., Зверев В. В. Оценка экспрессии генов компонентов врожденного иммунитета в лейкоцитах мышей при действии синтетических лигандов in vivo. Журнал микробиологии, эпидемиологии и иммунобиологии. 2013; 6: 76–80.

Labzhinov P. A., Svitich O. A., Gankovskaya L. V., Zverev V. V. Evaluation of expression of innate immunity component genes in mice leukocytes under the effect of synthetic ligands in vivo. Zhurnal mikrobiologii, epidemiilogii i immunologii. [Journal of Microbiology Epidemiology and Immunobiology]. 2013; 6: 76– 80 (in Russian).

Di Pasquale A., Preiss S., Tavares Da Silva F., Garcon N. Vaccine adjuvants: from 1920 to 2015 and beyond. Vaccines 2015; 3: 320–343.

Goubau D., Deddouche S., Reis e Sousa C. Cytosolic sensing of viruses. Immunity 2013; 38: 855–869.

Жигалкина П. В., Свитич О. А. Потенциальная роль регуляторных РНК (lncRNA) во врожденном иммунитете. В сборнике: Глобализация научных процессов сборник статей Международной научно-практической конференции. Киров; 2016: 9–12.

Zhigalkina P. V., Svitich O. A. The potential role of regulatory RNA (lncRNA) in innate immunity. V sbornike: Globalizatsiya nauchnyih protsessov sbornik statey Mezhdunarodnoy nauchno-prakticheskoy konferentsii. [In the collection: Globalization of scientific processes, a collection of articles of the International Scientific and Practical Conference]. Kirov; 2016: 9–12 (in Russian).

Huber J. P., Farrar D. J. Regulation of effector and memory T-cell functions by type I interferon. Immunology. 2011; 132: 466–474.

Лабжинов П. А. Оценка эффективности влияния синтетических лигандов TLRs на экспрессию генов TLR9 и BD-2 в лейкоцитах мышей линии BALB/C. В сборнике: Наука и современность сборник статей Международной научно-практической конференции. Сызрань; 2016: 9–12.

Labzhinov P. A. Evaluation of efficiency of synthetic TLRs ligands on the expression of TLR9 and BD-2 genes in leukocytes of BALB/C mice. V sbornike: Nauka i sovremennost sbornik statey Mezhdunarodnoy nauchno-prakticheskoy konferentsii. [In the collection: Science and modernity, a collection of articles of the International Scientific and Practical Conference]. Sizran; 2016: 9–12 (in Russian).

Кукина П. И., Свитич О. А. Новые подходы в оценке регуляции экспрессии генов TLR. В сборнике: Наука и современность сборник статей Международной научно-практической конференции. Сызрань; 2016: 6–9.

Kukina P. I., Svitich O. A. New approaches in evaluation of the regulation of TLR gene expression. V sbornike: Nauka i sovremennost sbornik statey Mezhdunarodnoy nauchno-prakticheskoy konferentsii. [In the collection: Science and modernity, a collection of articles of the International Scientific and Practical Conference]. Sizran; 2016: 6–9 (in Russian).

Mogensen T. H. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin. Microbiol. Rev. 2009; 22: 240–273.

Mifsud E. J., Tan A. C. L., Jackson D. C. TLR agonists as modulators of the innate immune response and their potential as agents against infectious disease. Front. Immunol. 2014; 5.

Ковальчук Л. В., Свитич О. А., Ганковская Л. В., Мироншиченкова А. М., Ганковский В. А. Роль toll-подобных рецепторов в патогенезе инфекционных заболеваний человека. Курский научно-практический вестник «Человек и его здоровье». 2012; 2: 147–153.

Kovalchuk L. V., Svitich O. A., Gankovskaya L. V., Miroshnichenkova A. M., Gankovskii V. A. The role of toll-like receptors in pathogenesis of human infection. Kurskiy nauchno-prakticheskiy vestnik «Chelovek i ego zdorove». [Kursk Scientific and Practical Bulletin «Man and His Health»]. 2012; 2: 147–153 (in Russian).

Dimmock N. J., Easton A. J. Defective interfering influenza virus RNAs: Time to reevaluate their clinical potential as broad-spectrum antivirals? J. Virol. 2014; 88: 5217–5227.

Dimmock N. J., Easton A. J. Defective interfering influenza virus RNAs: Time to reevaluate their clinical potential as broad-spectrum antivirals? J. Virol. 2014; 88: 5217 – 5227.

Gutjahr A., Tiraby G., Perouzel E., Verrier B., Paul S. Triggering Intracellular Receptors for Vaccine Adjuvantation. Trends Immunol. 2016; 37: 573–587.

Gutjahr A., Tiraby G., Perouzel E., Verrier B., Paul S. Triggering Intracellular Receptors for Vaccine Adjuvantation. Trends Immunol. 2016; 37: 573 – 587.

Apostolico J. D. S., Lunardelli V. A. S., Coirada F. C., Boscardin S. B., Rosa D. S. Adjuvants: classification, modus operandi, and licensing. J. Immunol. Res. 2016; 2016: 1–16.

Apostolico J.D.S., Lunardelli V.A.S., Coirada F.C., Boscardin S.B., Rosa D.S. Adjuvants: Classification, Modus Operandi, and Licensing. J. Immunol. Res. 2016; 2016: 1 – 16.

Hedayat M., Netea M. G., Rezaei N. Targeting of Toll-like receptors: A decade of progress in combating infectious diseases. Lancet Infect. Dis. 2011; 11: 702–712.

Hedayat M., Netea M.G., Rezaei N. Targeting of Toll-like receptors: A decade of progress in combating infectious diseases. Lancet Infect. Dis. 2011; 11: 702 – 712.

Dowling J. K., Mansell A. Toll-like receptors: The swiss army knife of immunity and vaccine development. Clin. Transl. Immunol. 2016; 5: e85.

Dowling J.K., Mansell A. Toll-like receptors: The swiss army knife of immunity and vaccine development. Clin. Transl. Immunol. 2016; 5: e85.

Kawai T., Akira S. TLR signaling. Cell Death Differ. 2006; 13: 816–825.

Kawai T., Akira S. TLR signaling. Cell Death Differ. 2006; 13: 816 – 825.

Ma Z., Zhang E., Yang D., Lu M. Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses. Cell. Mol. Immunol. 2015; 12: 273–282.

Лабжинов П. А. Влияние синтетических лигандов TLRs на показатели экспрессии генов TLR9 и BD-2 in vivo. В сборнике: Влияние науки на инновационное развитие сборник статей международной научно-практической конференции. Екатеринбург; 2017: 9–12.

Labzhinov P.A. Effect of synthetic TLRs ligands on the expression of TLR9 and BD-2 genes in vivo. V sbornike: Vliyanie nauki na innovatsionnoe razvitie sbornik statey mezhdunarodnoy nauchno-prakticheskoy konferentsii. [In the collection: The influence of science on innovative development, a collection of articles of an international scientific and practical conference]. Ekaterinburg; 2017: 9 – 12. (in Russian)

Garçon N., Chomez P., Van Mechelen M. GlaxoSmithKline Adjuvant Systems in vaccines: Concepts, achievements and perspectives. Expert Rev. Vaccines 2007; 6: 723–739.

Kester K. E., Cummings J. F., Ofori-Anyinam O., Ockenhouse C. F., Krzych U., Moris P. et al. Randomized, Double-Blind, Phase 2a trial of falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults: safety, efficacy, and immunologic associates of protection. J. Infect. Dis. 2009; 200: 337–346.

Leroux-Roels G., Leroux-Roels I., Clement F., Ofori-Anyinam O., Lievens M., Jongert E. et al. Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines: Randomized, double-blind study in malaria-naive adults. Hum. Vaccines Immunother. 2014; 10: 2211–2219.

Rosewich M., Lee D., Zielen S. Pollinex Quattro: An innovative four injections immunotherapy In allergic rhinitis. Hum. Vaccines Immunother. 2013; 9: 1523–1531.

Dupont J., Altclas J., Lepetic A., Lombardo M., Vázquez V., Salgueira C. et al. A controlled clinical trial comparing the safety and immunogenicity of a new adjuvanted hepatitis B vaccine with a standard hepatitis B vaccine. Vaccine 2006; 24: 7167–7174.

Lebwohl M., Dinehart S., Whiting D., Lee P. K., Tawfik N., Jorizzo J. et al. Imiquimod 5% cream for the treatment of actinic keratosis: Results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials. J. Am. Acad. Dermatol. 2004; 50: 714–721.

Krieg A. M. Therapeutic potential of Toll-like receptor 9 activation. Nat. Rev. Drug Discov. 2006; 5: 471–484.

Cooper C. L., Davis H. L., Morrris M. L., Efler S. M., Adhami M. A., Krieg A. M. et al. CPG 7909, an immunostimulatory tlr9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind Phase I/II study. J. Clin. Immunol. 2004; 24: 693–701.

Yu Y.-Z., Ma Y., Xu W.-H., Wang S., Sun Z.-W. Combinations of various CpG motifs cloned into plasmid backbone modulate and enhance protective immunity of viral replicon DNA anthrax vaccines. Med. Microbiol. Immunol. 2015; 204: 481–491.

Krieg A. M. Toll-like receptor 9 (TLR9) agonists in the treatment of cancer. Oncogene 2008; 27: 161–167.

Turley C. B., Rupp R. E., Johnson C., Taylor D. N., Wolfson J., Tussey L., Kavita U. et al.. Safety and immunogenicity of a recombinant M2e–flagellin influenza vaccine (STF2.4xM2e) in healthy adults. Vaccine 2011; 29: 5145–5152.

Longhi M. P., Trumpfheller C., Idoyaga J., Caskey M., Matos I., Kluger C. et al. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J. Exp. Med. 2009; 206: 1589–1602.

Gajewski T. F. Failure at the effector phase: Immune barriers at the level of the melanoma tumor microenvironment. Clin. Cancer Res. 2007; 13: 5256–5261.

Sun Y., Jain D., Koziol-White C. J., Genoyer E., Gilbert M., Tapia K. et al. Immunostimulatory defective viral genomes from respiratory syncytial virus promote a strong innate antiviral response during infection in mice and humans. PLoS Pathog. 2015; 11: e1005122.

Sun Y., Jain D., Koziol-White C. J., Genoyer E., Gilbert M., Tapia K. et al. Immunostimulatory Defective Viral Genomes from Respiratory Syncytial Virus Promote a Strong Innate Antiviral Response during Infection in Mice and Humans. PLoS Pathog. 2015; 11: e1005122.

Сергеев О. В. Рецепторные взаимодействия вируса клетки как начальный этап инфицирования. Вопросы вирусологии. 2011; 56 (4): 4–8.

ergeyev O. V. Receptor virus-cell interactions as an initial stage of infection. Voprosyi virusologii. [Problems of Virology]. 2011; 56(4): 4 – 8. (in Russian)

Marriott A. C., Dimmock N. J. Defective interfering viruses and their potential as antiviral agents. Rev. Med. Virol. 2010; 20: 51–62.

Yuan T. T., Lin M. H., Chen D. S., Shih C. A. defective interference-like phenomenon of human hepatitis B virus in chronic carriers. J. Virol. 1998; 72: 578–584.

Yuan T.T., Lin M.H., Chen D.S., Shih C. A. defective interference-like phenomenon of human hepatitis B virus in chronic carriers. J. Virol. 1998; 72: 578–584.

Li D., Lott W. B., Lowry K., Jones A., Thu H. M., Aaskov J. Defective interfering viral particles in acute dengue infections. PLoS ONE 2011; 6: e19447.

Saira K., Lin X., DePasse J. V., Halpin R., Twaddle A. Stockwell T. et al. Sequence analysis of in vivo defective interfering-like RNA of influenza A (H1N1) pandemic virus. J. Virol. 2013; 87: 8064–8074.

Saira K., Lin X., DePasse J. V., Halpin R., Twaddle A. Stockwell T. et al. Sequence Analysis of In Vivo Defective Interfering-Like RNA of Influenza A H1N1 Pandemic Virus. J. Virol. 2013; 87: 8064–8074.

Vasou A., Sultanoglu N., Goodbourn S., Randall R. E., Kostrikis L. G. Targeting pattern recognition receptors (PRR) for vaccine adjuvantation: from synthetic PRR agonists to the potential of defective interfering particles of viruses. Viruses. 2017; 9: 186.

Vasou A., Sultanoglu N., Goodbourn S., Randall R. E., Kostrikis L. G. Targeting Pattern Recognition Receptors (PRR) for Vaccine Adjuvantation: From Synthetic PRR Agonists to the Potential of Defective Interfering Particles of Viruses. Viruses. 2017; 9: 186.

Baum A., Sachidanandam R., Garcia-Sastre A. Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing. Proc. Nat. Acad. Sci. USA 2010; 107: 16303–16308.

Schoggins J. W., Rice C. M. Interferon-stimulated genes and their antiviral effector functions. Curr. Opin. Virol. 2011; 1: 519–525.

Schoggins J.W., Rice C.M. Interferon-stimulated genes and their antiviral effector functions. Curr. Opin. Virol. 2011; 1: 519–525.

Свитич О. А., Ковальчук Л. В., Банковская Л. В., Лавров В. Ф., Гервазиева В. Б., Парфенова Т. М., Конищева А. Ю., Головин Г. Г., Лабжинов П. А. Аналитический подход в изучении противовирусного и иммуномодулирующего действия препаратов на модели герпесвирусной инфекции in vitro. Российский иммунологический журнал. 2013; 7(4): 377 – 384.

Svitich O. A., Koval’chuk L. V., Gankovskaya L. V., Lavrov V. F., Gervazieva V. B., Parfenova T. M. et al. Analytical approach to study of antiviral and immunomodulating drugs on the model of herpes infection in vitro. Rossiyskiy immunologicheskiy zhurnal. [Russian Immunological Journal. 2013; 7 (4): 377–384 (in Russian).

Scott P. D., Meng B., Marriott A. C., Easton A. J., Dimmock N. J. Defective interfering influenza A virus protects in vivo against disease caused by a heterologous influenza B virus. J. Gen. Virol. 2011; 92: 2122–2132.

Besednova N. N., Makarenkova I. D., Zvyagintseva T. N., Imbs T. I., Somova L. M., Zaporozhets T. S. Antiviral activity and pathogenetic targets for seaweed sulfated polysaccharides in herpesvirus infections. Biochemistry (Moscow) Supplement. Series B: Biomedical Chemistry. 2016; 10(1): 31–42.

Фам Х. Ф., Сидоров А. В., Милованова А. В., Антонова Т. П., Лисаков А. Н., Нагиева Ф. Г. и др. В. Новый подход к диагностике varicella zoster-вирусной инфекции с использованием ПЦР в режиме реального времени. Эпидемиология и вакцинопрофилактика. 2016; 15 (5): 52–58.

Pham H. Ph., Sidorov A. V., Milovanova A. V., Antonova T. P., Lisakov A. N., Nagieva F. G. et al.. New Approach for Diagnostics of VZV Infection by Using Real-Time PCR. Epidemiologiya i vaktsinoprofilaktika. [Epidemiology and Vaccinal Prevention]. 2016; 15 (5): 52–58 (in Russian).

Killip M. J., Young D. F., Precious B. L., Goodbourn S., Randall R. E. Activation of the beta interferon promoter by paramyxoviruses in the absence of virus protein synthesis. J. Gen. Virol. 2012; 93: 299–307.

Killip M. J., Young D. F., Precious B. L., Goodbourn S., Randall R.E. Activation of the beta interferon promoter by paramyxoviruses in the absence of virus protein synthesis. J. Gen. Virol. 2012; 93: 299–307.

Yount J. S., Gitlin L., Moran T. M., López C. B. MDA5 participates in the detection of paramyxovirus infection and is essential for the early activation of dendritic cells in response to Sendai Virus defective interfering particles. J. Immunol. 2008; 180: 4910–4918.

Mercado-Lopez X., Cotter C. R., Kim W. K., Sun Y., Munoz L., Tapia K., Lopez C. B. Highly immunostimulatory RNA derived from a Sendai virus defective viral genome. Vaccine 2013; 31: 5713–5721.

Martínez-Gil L., Goff P. H., Hai R., García-Sastre A., Shaw M. L., Palese P. A Sendai virus-derived RNA agonist of RIG-I as a virus vaccine adjuvant. J. Virol. 2013; 87: 1290–1300.

Killip M. J., Young D. F., Ross C. S., Chen S., Goodbourn S., Randall R. E. Failure to activate the IFN-beta promoter by a paramyxovirus lacking an interferon antagonist. Virology 2011; 415: 39–46.

Killip M. J., Young D. F., Ross C. S., Chen S., Goodbourn S., Randall R.E. Failure to activate the IFN-beta promoter by a paramyxovirus lacking an interferon antagonist. Virology 2011; 415: 39–46.

McClure R., Massari P. TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens. Front. Immunol. 2014; 5: 386.

Wang J., Li P., Wu M. X. Natural STING Agonist as an «Ideal» adjuvant for cutaneous vaccination. J. Investig. Dermatol. 2016; 136: 2183–2191.

Wang J., Li P., Wu M.X. Natural STING Agonist as an «Ideal» adjuvant for cutaneous vaccination. J. Investig. Dermatol. 2016; 136: 2183 – 2191.

CDC. CDC’s Strategic Framework for Global Immunization, 2016–2020; CDC: Atlanta, GA, USA; 2016.

CDC. CDC’s Strategic Framework for Global Immunization, 2016–2020; CDC: Atlanta, GA, USA, 2016.

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