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Glycan Microarrays Containing Synthetic Streptococcus pneumoniae CPS Fragments and Their Application to Vaccine Development

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 2460))

Abstract

Streptococcus pneumoniae is the leading source of life-endangering diseases like pneumonia, septicemia, and meningitis, as well as a major cause of death in children under 5 years old in developing countries. At least 98 serotypes of S. pneumoniae can be distinguished based on their structurally distinct capsular polysaccharides (CPS). Currently available CPS-based pneumococcal vaccines contain serotypes most frequently associated with invasive pneumococcal diseases. The polysaccharides used in commercial conjugate-vaccines are isolated from bacteria cultures comprising many laborious and operationally challenging steps followed by depolymerization of long polysaccharides into small fragments and their conjugation to the carrier protein. The medicinal chemistry approach for glycoconjugate vaccine development offers an exciting alternative to CPS isolation for a broad range of different glycan antigens. Glycan arrays containing well-defined synthetic glycans of CPS fragments and repeating units are used as a platform for the high-throughput screening of various serum samples and identification of protective glycotopes for vaccine candidates.

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References

  1. Centers for Disease Control and Prevention (2016). Active Bacterial Core Surveillance (ABCs) Report: Emerging Infections Program Network, Streptococcus pneumoniae

    Google Scholar 

  2. Rodrigues CMC, Groves H (2018) Community-acquired pneumonia in children: the challenges of microbiological diagnosis. J Clin Microbiol 56(3):e01318-17. https://doi.org/10.1128/jcm.01318-17

    Article  PubMed  PubMed Central  Google Scholar 

  3. Klein Klouwenberg P, Bont L (2008) Neonatal and infantile immune responses to encapsulated bacteria and conjugate vaccines. Clin Dev Immunol 2008:628963. https://doi.org/10.1155/2008/628963

    Article  PubMed  PubMed Central  Google Scholar 

  4. Dretler AW, Rouphael NG, Stephens DS (2018) Progress toward the global control of Neisseria meningitidis: 21st century vaccines, current guidelines, and challenges for future vaccine development. Hum Vaccin Immunother 14(5):1–35. https://doi.org/10.1080/21645515.2018.1451810

    Article  Google Scholar 

  5. Society AT (2018). https://www.lung.org/assets/documents/research/pi-trend-report.pdf

  6. Cilloniz C, Dominedo C, Garcia-Vidal C, Torres A (2018) Community-acquired pneumonia as an emergency condition. Curr Opin Crit Care 24(6):531–539. https://doi.org/10.1097/mcc.0000000000000550

    Article  PubMed  Google Scholar 

  7. UNICEF (2017) Levels & trends in child mortality report 2017. The United Nations Children’s Fund, New York

    Google Scholar 

  8. Li Y, Weinberger DM, Thompson CM, Trzcinski K, Lipsitch M (2013) Surface charge of Streptococcus pneumoniae predicts serotype distribution. Infect Immun 81(12):4519–4524. https://doi.org/10.1128/iai.00724-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gruber WC, Scott DA, Emini EA (2012) Development and clinical evaluation of Prevnar 13, a 13-valent pneumococcal CRM197 conjugate vaccine. Ann N Y Acad Sci 1263:15–26. https://doi.org/10.1111/j.1749-6632.2012.06673.x

    Article  PubMed  Google Scholar 

  10. Ampofo K, Byington CL (2018) 123—Streptococcus pneumoniae. In: Long SS, Prober CG, Fischer M (eds) Principles and practice of pediatric infectious diseases, 5th edn. Elsevier, pp 737–746.e734. https://doi.org/10.1016/B978-0-323-40181-4.00123-7

    Chapter  Google Scholar 

  11. Geno KA, Gilbert GL, Song JY, Skovsted IC, Klugman KP, Jones C, Konradsen HB, Nahm MH (2015) Pneumococcal capsules and their types: past, present, and future. Clin Microbiol Rev 28(3):871–899. https://doi.org/10.1128/cmr.00024-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hayward S, Thompson LA, McEachern A (2016) Is 13-valent pneumococcal conjugate vaccine (PCV13) combined with 23-valent pneumococcal polysaccharide vaccine (PPSV23) superior to PPSV23 alone for reducing incidence or severity of pneumonia in older adults? A Clin-IQ. J Patient-Centered Res Rev 3(2):111–115. https://doi.org/10.17294/2330-0698.1214

    Article  Google Scholar 

  13. Principi N, Esposito S (2018) Development of pneumococcal vaccines over the last 10 years. Expert Opin Biol Ther 18(1):7–17. https://doi.org/10.1080/14712598.2018.1384462

    Article  CAS  PubMed  Google Scholar 

  14. Cole J, Aberdein J, Jubrail J, Dockrell DH (2014) Chapter Four—the role of macrophages in the innate immune response to Streptococcus pneumoniae and Staphylococcus aureus: mechanisms and contrasts. In: Poole RK (ed) Advances in microbial physiology, vol 65. Academic, pp 125–202. https://doi.org/10.1016/bs.ampbs.2014.08.004

    Chapter  Google Scholar 

  15. Miller E, Andrews NJ, Waight PA, Slack MPE, George RC (2011) Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study. Lancet Infect Dis 11(10):760–768. https://doi.org/10.1016/S1473-3099(11)70090-1

    Article  CAS  PubMed  Google Scholar 

  16. Synytsya A, Novak M (2014) Structural analysis of glucans. Ann Transl Med 2(2):17. https://doi.org/10.3978/j.issn.2305-5839.2014.02.07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. WHO (2000) Recommendations for the production and control of Haemophilus influenzae type b conjugate vaccines, volume 897. WHO

    Google Scholar 

  18. Guberman M, Seeberger PH (2019) Automated glycan assembly: a perspective. J Am Chem Soc 141(14):5581–5592. https://doi.org/10.1021/jacs.9b00638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Geissner A, Reinhardt A, Rademacher C, Johannssen T, Monteiro J, Lepenies B, Thepaut M, Fieschi F, Mrazkova J, Wimmerova M, Schuhmacher F, Gotze S, Grunstein D, Guo X, Hahm HS, Kandasamy J, Leonori D, Martin CE, Parameswarappa SG, Pasari S, Schlegel MK, Tanaka H, Xiao G, Yang Y, Pereira CL, Anish C, Seeberger PH (2019) Microbe-focused glycan array screening platform. Proc Natl Acad Sci U S A 116(6):1958–1967. https://doi.org/10.1073/pnas.1800853116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Geissner A, Anish C, Seeberger PH (2014) Glycan arrays as tools for infectious disease research. Curr Opin Chem Biol 18:38–45. https://doi.org/10.1016/j.cbpa.2013.11.013

    Article  CAS  PubMed  Google Scholar 

  21. Emmadi M, Khan N, Lykke L, Reppe K, Sharavathi GP, Lisboa MP, Wienhold SM, Witzenrath M, Pereira CL, Seeberger PH (2017) A Streptococcus pneumoniae type 2 oligosaccharide glycoconjugate elicits opsonic antibodies and is protective in an animal model of invasive pneumococcal disease. J Am Chem Soc 139(41):14783–14791. https://doi.org/10.1021/jacs.7b07836

    Article  CAS  PubMed  Google Scholar 

  22. Parameswarappa SG, Reppe K, Geissner A, Menova P, Govindan S, Calow AD, Wahlbrink A, Weishaupt MW, Monnanda BP, Bell RL, Pirofski LA, Suttorp N, Sander LE, Witzenrath M, Pereira CL, Anish C, Seeberger PH (2016) A semi-synthetic oligosaccharide conjugate vaccine candidate confers protection against Streptococcus pneumoniae serotype 3 infection. Cell Chem Biol 23(11):1407–1416. https://doi.org/10.1016/j.chembiol.2016.09.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lisboa MP, Khan N, Martin C, Xu FF, Reppe K, Geissner A, Govindan S, Witzenrath M, Pereira CL, Seeberger PH (2017) Semisynthetic glycoconjugate vaccine candidate against Streptococcus pneumoniae serotype 5. Proc Natl Acad Sci U S A 114(42):11063–11068. https://doi.org/10.1073/pnas.1706875114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Schumann B, Hahm HS, Parameswarappa SG, Reppe K, Wahlbrink A, Govindan S, Kaplonek P, Pirofski LA, Witzenrath M, Anish C, Pereira CL, Seeberger PH (2017) A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine. Sci Transl Med 9(380):eaaf5347. https://doi.org/10.1126/scitranslmed.aaf5347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Polonskaya Z, Deng S, 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 (2017) T cells control the generation of nanomolar-affinity anti-glycan antibodies. J Clin Invest 127(4):1491–1504. https://doi.org/10.1172/jci91192

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kurbatova EA, Akhmatova NK, Akhmatova EA, Egorova NB, Yastrebova NE, Sukhova EV, Yashunsky DV, Tsvetkov YE, Gening ML, Nifantiev NE (2017) Neoglycoconjugate of tetrasaccharide representing one repeating unit of the Streptococcus pneumoniae type 14 capsular polysaccharide induces the production of opsonizing IgG1 antibodies and possesses the highest protective activity as compared to hexa- and octasaccharide conjugates. Front Immunol 8:659. https://doi.org/10.3389/fimmu.2017.00659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kaplonek P, Khan N, Reppe K, Schumann B, Emmadi M, Lisboa MP, Xu FF, Calow ADJ, Parameswarappa SG, Witzenrath M, Pereira CL, Seeberger PH (2018) Improving vaccines against Streptococcus pneumoniae using synthetic glycans. Proc Natl Acad Sci U S A 115(52):13353–13358. https://doi.org/10.1073/pnas.1811862115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sun X, Stefanetti G, Berti F, Kasper DL (2019) Polysaccharide structure dictates mechanism of adaptive immune response to glycoconjugate vaccines. Proc Natl Acad Sci 116(1):193–198. https://doi.org/10.1073/pnas.1816401115

    Article  CAS  PubMed  Google Scholar 

  29. Benaissa-Trouw B, Lefeber DJ, Kamerling JP, Vliegenthart JF, Kraaijeveld K, Snippe H (2001) Synthetic polysaccharide type 3-related di-, tri-, and tetrasaccharide-CRM(197) conjugates induce protection against Streptococcus pneumoniae type 3 in mice. Infect Immun 69(7):4698–4701. https://doi.org/10.1128/iai.69.7.4698-4701.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Safari D, Dekker HA, Joosten JA, Michalik D, de Souza AC, Adamo R, Lahmann M, Sundgren A, Oscarson S, Kamerling JP, Snippe H (2008) Identification of the smallest structure capable of evoking opsonophagocytic antibodies against Streptococcus pneumoniae type 14. Infect Immun 76(10):4615–4623. https://doi.org/10.1128/iai.00472-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mazmanian SK, Kasper DL (2006) The love-hate relationship between bacterial polysaccharides and the host immune system. Nat Rev Immunol 6(11):849–858. https://doi.org/10.1038/nri1956

    Article  CAS  PubMed  Google Scholar 

  32. Avci FY, Li X, Tsuji M, Kasper DL (2013) Carbohydrates and T cells: a sweet twosome. Semin Immunol 25(2):146–151. https://doi.org/10.1016/j.smim.2013.05.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Berti F, Adamo R (2018) Antimicrobial glycoconjugate vaccines: an overview of classic and modern approaches for protein modification. Chem Soc Rev 47(24):9015–9025. https://doi.org/10.1039/c8cs00495a

    Article  CAS  PubMed  Google Scholar 

  34. Sun L, Middleton DR, Wantuch PL, Ozdilek A, Avci FY (2016) Carbohydrates as T-cell antigens with implications in health and disease. Glycobiology 26(10):1029–1040. https://doi.org/10.1093/glycob/cww062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Micoli F, Costantino P, Adamo R (2018) Potential targets for next generation anti-microbial glycoconjugate vaccines. FEMS Microbiol Rev 42(3):388–423. https://doi.org/10.1093/femsre/fuy011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank the Max Planck Society and the German Research Foundation (SFB/TR 84 “Innate Immunity of the Lung,” C3, C6, C8) for the financial support. We also appreciate the help of ZIBI Graduate School and International Max Planck Research School for Infectious Diseases and Immunology program (IMPRS-IDI).

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Correspondence to Peter H. Seeberger .

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Kaplonek, P., Seeberger, P.H. (2022). Glycan Microarrays Containing Synthetic Streptococcus pneumoniae CPS Fragments and Their Application to Vaccine Development. In: Kilcoyne, M., Gerlach, J.Q. (eds) Glycan Microarrays. Methods in Molecular Biology, vol 2460. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2148-6_12

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  • DOI: https://doi.org/10.1007/978-1-0716-2148-6_12

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  • Publisher Name: Humana, New York, NY

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