肺炎链球菌糖疫苗的研究进展
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国家自然科学基金(31770997,32070921);泰山产业领军人才工程专项经费


Carbohydrate-based vaccines of Streptococcus pneumoniae
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    摘要:

    肺炎链球菌(Streptococcus pneumoniae)是引起多种疾病的主要病原体,包括侵袭性感染(如败血症和脑膜炎菌血症),以及更常见的粘膜部位感染(如肺炎、中耳炎和鼻窦炎)。根据肺炎链球菌表面荚膜多糖结构的不同可以分成不同的血清型,至今已经鉴定出98种,其中有20种具有高毒力。为了预防肺炎链球菌感染,已研制出了多种相关疫苗。目前,常用的有23价肺炎链球菌多糖疫苗(23-valent pneumococcal polysaccharide vaccine,PPV23)和13价肺炎链球菌结合疫苗(13-valent pneumococcal protein-conjugate vaccine,PCV13)。然而,从天然来源纯化的多糖抗原面临着纯化困难和组成不均等问题,因此,基于合成寡糖的糖缀合物疫苗成为一种有前途的替代物。疫苗接种后出现了血清型替代和某些血清型(如3型、19A型)致病率升高的现象,因此血清非依赖性的蛋白疫苗和全细胞疫苗成为新的研究热点。本综述主要以3型肺炎链球菌疫苗为例,概述不同种类疫苗的作用机制及其研究进展。

    Abstract:

    Streptococcus pneumoniae causes a range of diseases such as invasive infections (bacteremia of septicemia and meningitis, etc.) and common mucosa infections (pneumonia, otitis media, sinusitis, etc.). According to the structure of surface capsular polysaccharide, it is classified into different serotypes (98 serotypes identified, with 20 highly virulent). A number of related vaccines have been developed, among which 23-valent pneumococcal polysaccharide vaccine (PPV23) and 13-valent pneumococcal protein-conjugate vaccine (PCV13) are commonly used. However, natural polysaccharide antigens face some challenges, such as difficulty in purification and uneven composition. Therefore, synthetic oligosaccharide-based glycoconjugate vaccines have become a promising alternative. After vaccination, serotype substitution occurs and the pathogenicity rate of certain serotypes (such as serotype 3 and 19A) increases. Thus, serum-independent protein vaccines and whole-cell vaccines have become a new research focus. This review took S. pneumoniae serotype 3 vaccine as an example to summarize the mechanism of different types of vaccines and their research progress.

    参考文献
    [1] Bogaert D, De Groot R, Hermans P. Streptococcus pneumoniae colonisation:the key to pneumococcal disease. The Lancet Infectious Diseases, 2004, 4(3):144-154.
    [2] Van Der Poll T, Opal SM. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet, 2009, 374(9700):1543-1556.
    [3] Weiser JN, Ferreira DM, Paton JC. Streptococcus pneumoniae:transmission, colonization and invasion. Nature Reviews Microbiology, 2018, 16(6):355-367.
    [4] Drijkoningen JJC, Rohde GGU. Pneumococcal infection in adults:burden of disease. Clinical Microbiology and Infection, 2014, 20(Suppl 5):45-51.
    [5] Luck JN, Tettelin H, Orihuela CJ. Sugar-coated killer:serotype 3 pneumococcal disease. Frontiers in Cellular and Infection Microbiology, 2020, 10:613287.
    [6] Brooks LRK, Mias GI. Streptococcus pneumonia's virulence and host immunity:aging, diagnostics, and prevention. Frontiers in Immunology, 2018, 9:1366.
    [7] Steel HC, Cockeran R, Anderson R, Feldman C. Overview of community-acquired pneumonia and the role of inflammatory mechanisms in the immunopathogenesis of severe pneumococcal disease. Mediators of Inflammation, 2013, 2013:490346.
    [8] Geno KA, Saad JS, Nahm MH. Discovery of novel pneumococcal serotype 35D, a natural WciG-deficient variant of serotype 35B. Journal of Clinical Microbiology, 2017, 55(5):1416-1425.
    [9] Paton JC, Trappetti C. Streptococcus pneumoniae capsular polysaccharide. Microbiology Spectrum, 2019, 7(2):DOI:10.1128/microbiolspec.gpp3-0019-2018.
    [10] Weinberger DM, Trzciński K, Lu YJ, Bogaert D, Brandes A, Galagan J, Anderson PW, Malley R, Lipsitch M. Pneumococcal capsular polysaccharide structure predicts serotype prevalence. PLoS Pathogens, 2009, 5(6):e1000476.
    [11] McDaniel LS, Swiatlo E. Pneumococcal disease. Infectious Diseases in Clinical Practice, 2004, 12(2):93-98.
    [12] MacLeod CM, Hodges RG. Prevention of pneumococcal pneumonia by immunization with specific capsular polysaccharides. The Journal of Experimental Medicine, 1945, 82:445-465.
    [13] Feldman C, Anderson R. Review:current and new generation pneumococcal vaccines. Journal of Infection, 2014, 69(4):309-325.
    [14] Wantuch PL, Avci FY. Invasive pneumococcal disease in relation to vaccine type serotypes. Human Vaccines & Immunotherapeutics, 2019, 15(4):874-875.
    [15] Parameswarappa SG, Reppe K, Geissner A, Ménová P, Govindan S, Calow ADJ, Wahlbrink A, Weishaupt MW, Monnanda BP, Bell RL, Pirofski LA, Suttorp N, Sander LE, Witzenrath M, Pereira CL, Anish C, Seeberger PH. A semi-synthetic oligosaccharide conjugate vaccine candidate confers protection against Streptococcus pneumoniae serotype 3 infection. Cell Chemical Biology, 2016, 23(11):1407-1416.
    [16] Principi N, Esposito S. Development of pneumococcal vaccines over the last 10 years. Expert Opinion on Biological Therapy, 2018, 18(1):7-17.
    [17] Avci FY, Kasper DL. How bacterial carbohydrates influence the adaptive immune system. Annual Review of Immunology, 2010, 28:107-130.
    [18] Weintraub A. Immunology of bacterial polysaccharide antigens. Carbohydrate Research, 2003, 338(23):2539-2547.
    [19] De Gregorio E, Rappuoli R. From empiricism to rational design:a personal perspective of the evolution of vaccine development. Nature Reviews Immunology, 2014, 14(7):505-514.
    [20] Bentley SD, Aanensen DM, Mavroidi A, Saunders D, Rabbinowitsch E, Collins M, Donohoe K, Harris D, Murphy L, Quail MA, Samuel G, Skovsted IC, Kaltoft MS, Barrell B, Reeves PR, Parkhill J, Spratt BG. Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes. PLoS Genetics, 2006, 2(3):e31.
    [21] Yother J. Capsules of Streptococcus pneumoniae and other bacteria:paradigms for polysaccharide biosynthesis and regulation. Annual Review of Microbiology, 2011, 65:563-581.
    [22] Forsee WT, Cartee RT, Yother J. A kinetic model for chain length modulation of Streptococcus pneumoniae cellubiuronan capsular polysaccharide by nucleotide sugar donor concentrations. Journal of Biological Chemistry, 2009, 284(18):11836-11844.
    [23] Cartee RT, Forsee WT, Schutzbach JS, Yother J. Mechanism of type 3 capsular polysaccharide synthesis in Streptococcus pneumoniae. Journal of Biological Chemistry, 2000, 275(6):3907-3914.
    [24] Forsee WT, Cartee RT, Yother J. Characterization of the lipid linkage region and chain length of the cellubiuronic acid capsule of Streptococcus pneumoniae. The Journal of Biological Chemistry, 2009, 284(18):11826-11835.
    [25] Geno KA, Gilbert GL, Song JY, Skovsted IC, Klugman KP, Jones C, Konradsen HB, Nahm MH. Pneumococcal capsules and their types:past, present, and future. Clinical Microbiology Reviews, 2015, 28(3):871-899.
    [26] Cartee RT, Forsee WT, Jensen JW, Yother J. Expression of the Streptococcus pneumoniae type 3 synthase in Escherichia coli. Assembly of type 3 polysaccharide on a lipid primer. The Journal of Biological Chemistry, 2001, 276(52):48831-48839.
    [27] Smith CM, Fry SC, Gough KC, Patel AJ, Glenn S, Goldrick M, Roberts IS, Whitelam GC, Andrew PW. Recombinant plants provide a new approach to the production of bacterial polysaccharide for vaccines. PLoS One, 2014, 9(2):e88144.
    [28] Gilbert C, Robinson K, Le Page RW, Wells JM. Heterologous expression of an immunogenic pneumococcal type 3 capsular polysaccharide in Lactococcus lactis. Infection and Immunity, 2000, 68(6):3251-3260.
    [29] 程亚慧, 沈荣, 乔瑞洁. 细菌性多糖蛋白结合疫苗免疫应答机制的研究进展. 微生物学免疫学进展, 2018, 46(4):81-86. Cheng YH, Shen R, Qiao RJ. Advances on immune response mechanisms of bacterial glyco-conjugate vaccines. Progress in Microbiology and Immunology, 2018, 46(4):81-86. (in Chinese)
    [30] Avci FY, Li XM, Tsuji M, Kasper DL. A mechanism for glycoconjugate vaccine activation of the adaptive immune system and its implications for vaccine design. Nature Medicine, 2011, 17(12):1602-1609.
    [31] Rappuoli R, De Gregorio E. A sweet T cell response. Nature Medicine, 2011, 17(12):1551-1552.
    [32] Zimmermann S, Lepenies B. Glycans as vaccine antigens and adjuvants:immunological considerations. Carbohydrate-Based Vaccines, 2015, 1331:11-26.
    [33] Adamo R, Nilo A, Castagner B, Boutureira O, Berti F, Bernardes GJL. Synthetically defined glycoprotein vaccines:current status and future directions. Chemical Science, 2013, 4(8):2995-3008.
    [34] Rappuoli R, De Gregorio E, Costantino P. On the mechanisms of conjugate vaccines. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116(1):14-16.
    [35] 张涛, 孟欣, 朱涛, 刘正, 张立平, 郝杰清. 3型肺炎球菌荚膜多糖结合疫苗的研制. 中国免疫学杂志, 2015, 31(10):1361-1365. Zhang T, Meng X, Zhu T, Liu Z, Zhang LP, Hao JQ. Preparation of Streptococcus pneumonia type 3 capsular polysaccharide conjugate vaccine. Chinese Journal of Immunology, 2015, 31(10):1361-1365. (in Chinese)
    [36] Berti F, Adamo R. Recent mechanistic insights on glycoconjugate vaccines and future perspectives. ACS Chemical Biology, 2013, 8(8):1653-1663.
    [37] Verez-Bencomo V, Fernández-Santana V, Hardy E, Toledo ME, Rodríguez MC, Heynngnezz L, Rodriguez A, Baly A, Herrera L, Izquierdo M, Villar A, Valdés Y, Cosme K, Deler ML, Montane M, Garcia E, Ramos A, Aguilar A, Medina E, Toraño G, Sosa I, Hernandez I, Martínez R, Muzachio A, Carmenates A, Costa L, Cardoso F, Campa C, Diaz M, Roy R. A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type B. Science, 2004, 305(5683):522-525.
    [38] Astronomo RD, Burton DR. Carbohydrate vaccines:developing sweet solutions to sticky situations? Nature Reviews Drug Discovery, 2010, 9(4):308-324.
    [39] Anish C, Schumann B, Pereira CL, Seeberger PH. Chemical biology approaches to designing defined carbohydrate vaccines. Chemistry & Biology, 2014, 21(1):38-50.
    [40] Morelli L, Poletti L, Lay L. Carbohydrates and immunology:synthetic oligosaccharide antigens for vaccine formulation. European Journal of Organic Chemistry, 2011, 2011(29):5723-5777.
    [41] Pellicci DG, Clarke AJ, Patel O, Mallevaey T, Beddoe T, Le Nours J, Uldrich AP, McCluskey J, Besra GS, Porcelli SA, Gapin L, Godfrey DI, Rossjohn J. Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors. Nature Immunology, 2011, 12(9):827-833.
    [42] Deck MB, Sjölin P, Unanue ER, Kihlberg J. MHC-restricted, glycopeptide-specific T cells show specificity for both carbohydrate and peptide residues. Journal of Immunology, 1999, 162(8):4740-4744.
    [43] Mogemark M, Cirrito TP, Sjölin P, Unanue ER, Kihlberg J. Influence of saccharide size on the cellular immune response to glycopeptides. Organic & Biomolecular Chemistry, 2003, 1(12):2063-2069.
    [44] Kabat EA. The upper limit for the size of the human antidextran combining site. Journal of Immunology, 1960, 84:82-85.
    [45] Polonskaya Z, Deng SL, Sarkar A, Kain L, Comellas-Aragones M, McKay CS, Kaczanowska K, Holt M, McBride R, Palomo V, Self KM, Taylor S, Irimia A, Mehta SR, Dan JM, Brigger M, Crotty S, Schoenberger SP, Paulson JC, Wilson IA, Savage PB, Finn MG, Teyton L. T cells control the generation of nanomolar-affinity anti-glycan antibodies. The Journal of Clinical Investigation, 2017, 127(4):1491-1504.
    [46] Feng SJ, Xiong CH, Wang SB, Guo ZW, Gu GF. Semisynthetic glycoconjugate vaccines to elicit T cell-mediated immune responses and protection against Streptococcus pneumoniae serotype 3. ACS Infectious Diseases, 2019, 5(8):1423-1432.
    [47] Benaissa-Trouw B, Lefeber DJ, Kamerling JP, Vliegenthart JFG, Kraaijeveld K, Snippe H. Synthetic polysaccharide type 3-related di-, tri-, and tetrasaccharide-CRM 197 conjugates induce protection against Streptococcus pneumoniae type 3 in mice. Infection and Immunity, 2001, 69(7):4698-4701.
    [48] Musher DM. How effective is vaccination in preventing pneumococcal disease? Infectious Disease Clinics of North America, 2013, 27(1):229-241.
    [49] Kurbatova EA, Akhmatova NK, Zaytsev AE, Akhmatova EA, Egorova NB, Yastrebova NE, Sukhova EV, Yashunsky DV, Tsvetkov YE, Nifantiev NE. Higher cytokine and opsonizing antibody production induced by bovine serum albumin (BSA)-conjugated tetrasaccharide related to Streptococcus pneumoniae type 3 capsular polysaccharide. Frontiers in Immunology, 2020, 11:578019.
    [50] Kaplonek P, Khan N, Reppe K, Schumann B, Emmadi M, Lisboa MP, Xu FF, Calow ADJ, Parameswarappa SG, Witzenrath M, Pereira CL, Seeberger PH. Improving vaccines against Streptococcus pneumoniae using synthetic glycans. Proceedings of the National Academy of Sciences of the United States of America, 2018, 115(52):13353-13358.
    [51] Falup-Pecurariu O. Lessons learnt after the introduction of the seven valent-pneumococcal conjugate vaccine toward broader spectrum conjugate vaccines. Biomedical Journal, 2012, 35(6):450.
    [52] Postma DF, Van Werkhoven CH, Huijts SM, Bolkenbaas M, Oosterheert JJ, Bonten MJM. New trends in the prevention and management of community-acquired pneumonia. The Netherlands Journal of Medicine, 2012, 70(8):337-348.
    [53] Miyaji EN, Oliveira MLS, Carvalho E, Ho PL. Serotype-independent pneumococcal vaccines. Cellular and Molecular Life Sciences, 2013, 70(18):3303-3326.
    [54] Ginsburg AS, Alderson MR. New conjugate vaccines for the prevention of pneumococcal disease in developing countries. Drugs of Today, 2011, 47(3):207.
    [55] Balsells E, Guillot L, Nair H, Kyaw MH. Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era:a systematic review and meta-analysis. PLoS One, 2017, 12(5):e0177113.
    [56] Hanquet G, Krizova P, Valentiner-Branth P, Ladhani SN, Nuorti JP, Lepoutre A, Mereckiene J, Knol M, Winje BA, Ciruela P, Ordobas M, Guevara M, McDonald E, Morfeldt E, Kozakova J, Slotved HC, Fry NK, Rinta-Kokko H, Varon E, Corcoran M, Van Der Ende A, Vestrheim DF, Munoz-Almagro C, Latasa P, Castilla J, Smith A, Henriques-Normark B, Whittaker R, Pastore Celentano L, Savulescu C, Group SM Pneumo. Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries:implications for adult vaccination. Thorax, 2019, 74(5):473-482.
    [57] Savulescu C, Krizova P, Lepoutre A, Mereckiene J, Vestrheim DF, Ciruela P, Ordobas M, Guevara M, McDonald E, Morfeldt E, Kozakova J, Varon E, Cotter S, Winje BA, Munoz-Almagro C, Garcia L, Castilla J, Smith A, Hanquet G. Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries:an observational multicentre study. The Lancet Respiratory Medicine, 2017, 5(8):648-656.
    [58] Jiang HF, Meng Q, Liu XR, Chen HY, Zhu CQ, Chen YS. PspA diversity, serotype distribution and antimicrobial resistance of invasive pneumococcal isolates from paediatric patients in Shenzhen, China. Infection and Drug Resistance, 2021, 14:49-58.
    [59] Mettu R, Chen CY, Wu CY. Synthetic carbohydrate- based vaccines:challenges and opportunities. Journal of Biomedical Science, 2020, 27(1):1-22.
    [60] Colombo C, Pitirollo O, Lay L. Recent advances in the synthesis of glycoconjugates for vaccine development. Molecules, 2018, 23(7):1712.
    [61] Moffitt K, Malley R. Rationale and prospects for novel pneumococcal vaccines. Human Vaccines & Immunotherapeutics, 2016, 12(2):383-392.
    [62] Middleton DR, Paschall AV, Duke JA, Avci FY. Enzymatic hydrolysis of pneumococcal capsular polysaccharide renders the bacterium vulnerable to host defense. Infection and Immunity, 2018, 86(8):e00316-18.
    [63] Paschall AV, Middleton DR, Wantuch PL, Avci FY. Therapeutic activity of type 3Streptococcus pneumoniae capsule degrading enzyme Pn3Pase. Pharmaceutical Research, 2020, 37(12):1-9.
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刘小宇,陈敏. 肺炎链球菌糖疫苗的研究进展[J]. 微生物学报, 2022, 62(2): 446-457

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  • 收稿日期:2021-04-30
  • 最后修改日期:2021-08-18
  • 在线发布日期: 2022-01-28
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