Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-7613Central Research Institute for Epidemiology41710.36233/0372-9311-2018-3-74-80REVIEWSОБЗОРЫTHE ROLE OF PROTEINS OF STREPTOCOCCUS PNEUMONIAE IN THE DEVELOPMENT OF SEROTYPE-INDEPENDENT PNEUMOCOCCAL VACCINESРОЛЬ БЕЛКОВ STREPTOCOCCUS PNEUMONIAE В РАЗРАБОТКЕ СЕРОТИП-НЕЗАВИСИМЫХ ПНЕВМОКОККОВЫХ ВАКЦИНPetukhovaE. S.ПетуховаЕ. С.
Russian Federation

Moscow

105064, Москва, М. Казенный пер., 5а

(495)917-57-74

VorobyevD. S.ВоробьевД. С.
Russian Federation

Moscow

Москва

SemenovaI. B.СеменоваИ. Б.
Russian Federation

Moscow

Москва

Mechnikov Research Institute of Vaccines and SeraНИИ вакцин и сывороток им. И.И.МечниковаSechenov First Moscow State Medical UniversityПервый Московский государственный медицинский университет им. И.М.Сеченова2507201895374802508201925082019Copyright ©; 2018, Petukhova E.S., Vorobyev D.S., Semenova I.B.Copyright ©; 2018, Петухова Е.С., Воробьев Д.С., Семенова И.Б.2018Petukhova E.S., Vorobyev D.S., Semenova I.B.Петухова Е.С., Воробьев Д.С., Семенова И.Б.https://creativecommons.org/licenses/by/4.0https://microbiol.crie.ru/jour/article/view/417

Infections caused by Streptococcus pneumoniae are relevant for Russia and the world. One of the key factors in the pathogenicity of pneumococcus is a polysaccharide capsule. The structure of polysaccharide antigens is described more than 90 serotypes of the pathogen. The experience of using polysaccharide and conjugated pneumococcal vaccines shows that these preventive drugs protect against a limited number of serotypes of the pneumococcus. It is of interest to study the protective properties of pneumococcal proteins, as they are conservative and have high homology within the species, potentially expanding serotype non-specific protection level. Thus, the efforts of researchers focus on the development of protein vaccines or conjugated vaccines based on proteins of S. pneumoniae. The review considers the biological properties of the most well-known proteins of pneumococcus and provides data on preclinical studies of the obtained recombinant proteins as experimental vaccine preparations. Immunization with various proteins of S. pneumoniae provides protection of animals from nasopharyngeal colonization, pneumonia and sepsis. Currently, clinical trials (I/II phases) are being tested with several experimental protein vaccines. In the near future it will be possible to assess the real effectiveness of such vaccines.

Инфекции, вызванные Streptococcus pneumoniae, являются актуальными для России и всего мира. Одним из ключевых факторов патогенности пневмококка считается полисахаридная капсула. По строению полисахаридных антигенов описано более 90 серотипов патогена. Опыт применения полисахаридных и конъюгированных пневмококковых вакцин показывает, что данные профилактические препараты защищают от ограниченного числа серотипов возбудителя. Представляет интерес исследование протективных свойств белков пневмококка, так как они консервативны и обладают высокой гомологией внутри вида, что потенциально расширяет спектр защиты от патогена. Таким образом, в настоящее время усилия исследователей сосредоточены на разработке белковых вакцин или конъюгированных вакцин на основе белков S. pneumoniae. В обзоре рассмотрены биологические свойства наиболее известных белков пневмококка и приведены данные о доклинических исследованиях полученных рекомбинантных белков в качестве экспериментальных вакцинных препаратов. Иммунизация различными белками S. pneumoniae обеспечивает защиту животных от назофарингеальной колонизации, пневмонии и сепсиса. В настоящее время с несколькими экспериментальными белковыми вакцинами проводят клинические испытания (I/II фазы). В ближайшем будущем можно будет оценить реальную эффективность таких вакцин.

Streptococcus pneumoniaepneumococcal proteinspneumococcal vaccineserotypeindependent protectionpreclinical studiesclinical trialsStreptococcus pneumoniaeпневмококковые белкипневмококковая вакцинасеротипнезависимая защитадоклинические исследованияклинические испытания1. Воробьев Д.С., Семенова И.Б., Курбатова Е.А. Белки Streptococcus pneumoniae: перспективы создания вакцины против пневмококковой инфекции. Журн. микробиол. 2010, 6: 98-104.2. Семенова И.Б., Михайлова Н.А. Серотипнезависимые вакцины против пневмококковой инфекции. Журн. микробиол. 2016, 4: 76-85.3. Alexander J.E., Lock R.A., Peeters C.A.M. et al. Immunization of mice with pneumolysin toxoid confers a significant degree of protection against at least nine serotypes of Streptococcus pneumoniae. Infect. Immun. 1994, 62 (12): 5683-5688.4. Alonso Develasco E., Verheul A.F.M., Verhoef J. et al. Streptococcus pneumoniae: virulence factors, pathogenesis, and vaccines. Microbiol. Reviews. 1995, 59 (4): 591-603.5. Biesbroek G., Wang X., Keijser B.J. et al. Seven-valent pneumococcal conjugate vaccine and nasopharyngeal microbiota in healthy children. Emerg. Infect. Dis. 2014, 20 (2): 201-210.6. Brown J.C., Ogunniyi A.D., Woodrow M.C. et al. Immunization with components of two iron uptake ABC transporters protects mice against systemic Streptococcus pneumoniae infection. Infect. Immun. 2001, 69 (11): 6702-6704.7. Daniels C.C., Coan P., King J. et al. The proline rich region of pneumococcal surface protein A and C contains surface accessible epitopes common to all pneumococci and elicits antibody mediated protection against sepsis. Infect. Immun. 2010, 78 (5): 2163-2172.8. Darriex M., Goulart C., Briles D. et al. Current status and perspectives on protein-based pneumococcal vaccines. Crit. Rev. Microbiol. 2013, DOI: 10.3109/1040841X.2013.813902.9. Darriex M., Miyaji E.N., Ferreira D.M. et al. Fusion proteins containing family 1 and family 2 PspA fragments elicit protection against Streptococcus pneumoniae that correlates with antibody mediated enhancement of complement deposition. Infect. Immun. 2007, 75 (12): 5930-5938.10. Dave S., Brooks-Walter A., Pangburn M.K. et al. Pspc, a pneumococcal surface protein, binds human factor H. Infect. Immun. 2001, 69 (5): 3435-3437.11. Feldman C., Anderson R. Review: Current and new generation pneumococcal vaccines, J. Infect. 2014, DOI: 10.1016/j.jinf.2014.06.006.12. Giefring C., Meinke A.L., Hanner M. et al. Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies. J. Exp. Med. 2008, 205 (1): 117-131.13. Ginsburg A.S., Nahm M.H., Khambaty F.M. et al. Issues and challenges in the development of pneumococcal protein vaccines: a two day international symposium, Expert. Rev. Vaccines. 2012, 11 (3): 279-285.14. Glover D.T., Hollingshead S.K., Briles D.E. Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsis. Infect. Immun. 2008, 76 (6): 2767-2776.15. Godfroid F., Hermand P., Verlant V. et al. Preclinical evaluation of the Pht proteins as potential cross-protective pneumococcal vaccine antigens. Infect. Immun. 2011, 79 (1): 238-245.16. Harfouche C., Filippini S., Gianfaldoni C. et al. RrgB321, a fusion protein of the three variants of the pneumococcal pilus backbone RrgB, is protective in vivo and elicits opsonic antibodies. Infect. Immun. 2012, 80 (1): 451-460.17. Iannelli F., Oggioni M.R., Pozzi G. Allelic variation in the highly polymorphic locus pspC of Streptococcus pneumoniae. Gene. 2002, 284: 63–71.18. Jackson L.A., Janoff E.N. Pneumococcal vaccination of elderly adults: new paradigm for protection. Clin. Infect. Dis. 2008, 47: 1328-1338.19. Johnson S.E., Dykes J.K., Jue D.L. et al. Inhibition of pneumococcal carriage in mice by subcutaneous immunization with peptides from the common surface protein pneumococcal surface adhesion A. J. Infect. Dis. 2002, 185: 489-496.20. Khan M.N., Pichichero M.E. Vaccine candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans. Vaccine. 2012, 30 (18): 2900-2907.21. Khan M.N., Sharma S.K., Filkins L.M. et al. PcpA of Streptococcus pneumoniae mediates adherence to nasopharyngeal and lung epithelial cells and elicits functional antibodies in humans. Microbes Infect. 2012, 14 (12): 1102-1110.22. Khan N., Jan A.T. Towards identifying protective B-cell epitopes: the PspA story. Front. Microbiol. 2017, 8: 742.23. King S.J., Hippe K.R., Weiser J.N. Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniae. Mol. Microbiol. 2006, 59 (3): 961-974.24. Long J.P., Tong H.H., DeMaria T.F. Immunization with native or recombinant Streptococcus pneumoniae neuraminidase affords protection in the chinchilla otitis media model. Infect. Immun. 2004, 72 (7): 4309-4313.25. Manco S., Hernon F., Yesilkaya H., et al. Pneumococcal neuraminidases A and B both have essential roles during infection of the respiratory tract and sepsis. Infect. Immun. 2006, 74 (7): 4014-4020.26. Mills M.F., Marquart M.E., Mcdaniel L.S. Localization of PcsB of Streptococcus pneumoniae and its differential expression in response to stress. J. Bacteriol. 2007, 189 (12): 4544-4546.27. Oloo E.O., Yethan J.A., Ochs M.M. et al. Structure guided antigen engineering yields pneumolysin mutants suitable for vaccination against pneumococcal disease. J. Biol. Chem. 2011, 286 (14): 12133-12140.28. Paton J.C., Lock R.A., Hansman D.J. Effect of immunization with pneumolysin on survival time of mice challenged with Streptococcus pneumoniae. Infect. Immun. 1983, 40 (2): 548-552.29. Perez-Dorado I., Galan-Bartual S., Hermoso J.A. Pneumococcal surface proteins: when the whole is greater than the sum of its parts. Molecular Oral Microbiology. 2012, 27: 221-245.30. Piao Z., Akeda Y., Takeuchi D., et al. Protective properties of a fusion pneumococcal surface protein A (PspA) vaccine against pneumococcal challenge by five different PspA clades in mice. Vaccine. 2014, 32: 5607-5613.31. Plumptre C.D., Ogunniyi A.D., Paton J.C. Surface association of Pht proteins of Streptococcus pneumoniae. Infect. Immun. 2013, 81 (10): 3644-3651.32. Principi N., Esposito S. Development of pneumococcal vaccines over the last 10 years. Expert. Opin. Biol. Ther. 2018, 18 (1): 7-17. Doi: 10.1080/14712598.2018.1384462. Epub 2017 Oct 12.33. Roche H., Ren B., McDaniel L.S. et al. Relative role of genetic background and variation in PspA in the ability of antibodies to PspA to protect against capsular type 3 and 4 strains of Streptococcus pneumoniae. Infect. Immun. 2003, 71 (8): 4498-4505.34. Romero-Steiner S., Pilshvili T., Sampson J.S. et al. Inhibition of pneumococcal adherence to human nasopharyngeal epithelial cells by anti-PsaA antibodies. Clin. Diagn. Lab. Immunol. 2003, 10 (2): 246-251.35. Selva L., Ciruela P., Blanchette K. et al. Prevalence and clonal distribution of PcpA, PsrP and Pilus-1 among pediatric isolates of Streptococcus pneumoniae. PLoS One. 2012, 7 (7): e41587.36. Sings H.L. Pneumococcal conjugate vaccine use in adults — Addressing an unmet medical need for non-bacteremic pneumococcal pneumonia. Vaccine. 2017, http://dx.doi.org/10.1016/j.vaccine.2017.05.075.37. Tarahomjoo S. Resent approaches in vaccine development against Streptococcus pneumoniae. J. Mol. Microbiol. Biotechnol. 2014, 24: 215-227.38. Vernatter J., Pirofski L.A. Current concepts in host-microbe interaction leading to pneumococcal pneumonia. Curr. Opin. Infect. Dis. 2013, 26 (3): 277-283.39. Yuan Z.Q., Lv Z.Y., Gan H.Q. et al. Intranasal immunization with autolysin (LytA) in mice model induced protection against five prevalent Streptococcus pneumoniae serotypes in China. Immunol. Res. 2011, 51: 108-115.