Vaccination against Pathogenic Bacteria: An Insight into Polysaccharide and Conjugate Vaccines
Abstract
Background: The cellular glycocalyx, a dense and complex coating of glycans, surrounds the surface of cells and serves as a critical interface between the cell and its external environment. Within this glycocalyx, the intricate glycans play essential roles in a variety of biological processes, including mediating cell-cell interactions, facilitating bacterial pathogenicity, and providing protection against environmental stressors such as desiccation, immune responses, and antimicrobial agents. The polysaccharides found on the outer surface of bacterial cells are particularly noteworthy due to their high degree of conservation across species and their easy accessibility. These characteristics make them excellent targets for immunological purposes, as they can be readily recognized by the immune system. As a result, bacterial polysaccharides and their repetitive units have been extensively studied and utilized as antigens in the development of vaccines with antibacterial properties. These vaccines leverage the unique structural features of polysaccharides to elicit robust and specific immune responses, offering a promising strategy for combating bacterial infections and enhancing public health.
Conclusion: In conclusion, it is important to emphasize that the topic explored in this article is vast, and the research field has experienced rapid growth in recent decades with ongoing advancements. Given the breadth of this field, it is challenging to cover the entire spectrum of polysaccharide-based bacterial vaccines targeting all bacterial pathogens. Additionally, due to inherent limitations, it was not feasible to include all research on polysaccharide and glycoconjugate vaccine development for a comprehensive set of bacterial pathogens. Therefore, only a subset of common bacteria and related vaccine development efforts have been evaluated in this discussion. Despite these limitations, the progress made in this area underscores the potential of polysaccharide-based vaccines as a powerful tool in the fight against bacterial infections.
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21. Micoli F, Costantino P, Adamo R. Potential targets for next generation antimicrobial glycoconjugate vaccines. FEMS Microbiol Rev 2018; 42(3):388-423.
22. Zhao Y, Wang S, Wang G, et al. Synthesis and immunological studies of group A Streptococcus cell-wall oligosaccharide–streptococcal C5a peptidase conjugates as bivalent vaccines. Organic Chemistry Frontiers 2019; 6(20):3589-96.
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24. MacCalman TE, Phillips-Jones MK, Harding SE. Glycoconjugate vaccines: some observations on carrier and production methods. Biotechnol Genet Eng Rev 2019; 35(2):93-125.
25. Dondoni A, Marra A. Recent applications of thiol-ene coupling as a click process for glycoconjugation. Chem Soc Rev 2012; 41(2):573-86.
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27. Cuccui J, Wren B. Hijacking bacterial glycosylation for the production of glycoconjugates, from vaccines to humanised glycoproteins. J Pharm Pharmacol 2015; 67(3):338-50.
28. Bugya Z, Prechl J, Szénási T, et al. Multiple levels of immunological memory and their association with vaccination. Vaccines (Basel). 2021; 9(2).
29. Anderluh M, Berti F, Bzducha-Wróbel A, et al. Recent advances on smart glycoconjugate vaccines in infections and cancer. Febs j 2022; 289(14):4251-303.
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3. Micoli F, Bagnoli F, Rappuoli R, et al. The role of vaccines in combatting antimicrobial resistance. Nature Rev Microbiol 2021; 19(5):287-302.
4. Rohokale R, Guo Z. Development in the concept of bacterial polysaccharide repeating unit-based antibacterial conjugate vaccines. ACS Infect Dis 2023; 9(2):178-212.
5. Cobb BA, Wang Q, Tzianabos AO, et al. Polysaccharide processing and presentation by the MHCII pathway. Cell 2004; 117(5):677-87.
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8. https://www.who.int/publications/i/item/9789240052451.
9. Micoli F, Del Bino L, Alfini R, et al. Glycoconjugate vaccines: current approaches towards faster vaccine design. Expert Rev Vaccines 2019; 18(9):881-95.
10. Soliman C, Pier GB, Ramsland PA. Antibody recognition of bacterial surfaces and extracellular polysaccharides. Curr Opin Struct Biol 2020; 62:48-55.
11. Stefanetti G, Borriello F, Richichi B, et al. Immunobiology of carbohydrates: implications for novel vaccine and adjuvant design against infectious diseases. Front Cell Infect Microbiol 2021; 11:808005.
12. Mettu R, Chen CY, Wu CY. Synthetic carbohydrate-based vaccines: challenges and opportunities. J Biomed Sci 2020; 27(1):9.
13. Zasłona ME, Downey AM, Seeberger PH, et al. Semi- and fully synthetic carbohydrate vaccines against pathogenic bacteria: recent developments. Biochem Soc Trans 2021; 49(5):2411-29.
14. Seeberger PH. Discovery of Semi- and fully-synthetic carbohydrate vaccines against bacterial infections using a medicinal chemistry approach. Chem Rev 2021; 121(7):3598-626.
15. Micoli F, Adamo R, Costantino P. Protein carriers for glycoconjugate vaccines: history, selection criteria, characterization and new trends. Molecules 2018; 23(6).
16. Avci F, Berti F, Dull P, et al. Glycoconjugates: what it would take to master these well-known yet little-understood immunogens for vaccine development. mSphere 2019; 4(5).
17. Schumann B, Hahm HS, Parameswarappa SG, et al. A semisynthetic Streptococcus pneumoniae serotype 8 glycoconjugate vaccine. Sci Transl Med 2017; 9(380).
18. van der Put RMF, Metz B, Pieters RJ. Carriers and antigens: new developments in glycoconjugate vaccines. Vaccines (Basel). 2023;11(2).
19. Zhang Q, Overkleeft HS, van der Marel GA, et al. Synthetic zwitterionic polysaccharides. Curr Opin Chem Biol 2017; 40:95-101.
20. Micoli F, Stefanetti G, MacLennan CA. Exploring the variables influencing the immune response of traditional and innovative glycoconjugate vaccines. Front Mol Biosci 2023; 10:1201693.
21. Micoli F, Costantino P, Adamo R. Potential targets for next generation antimicrobial glycoconjugate vaccines. FEMS Microbiol Rev 2018; 42(3):388-423.
22. Zhao Y, Wang S, Wang G, et al. Synthesis and immunological studies of group A Streptococcus cell-wall oligosaccharide–streptococcal C5a peptidase conjugates as bivalent vaccines. Organic Chemistry Frontiers 2019; 6(20):3589-96.
23. Anish C, Beurret M, Poolman J. Combined effects of glycan chain length and linkage type on the immunogenicity of glycoconjugate vaccines. npj Vaccines 2021; 6(1):150.
24. MacCalman TE, Phillips-Jones MK, Harding SE. Glycoconjugate vaccines: some observations on carrier and production methods. Biotechnol Genet Eng Rev 2019; 35(2):93-125.
25. Dondoni A, Marra A. Recent applications of thiol-ene coupling as a click process for glycoconjugation. Chem Soc Rev 2012; 41(2):573-86.
26. Lu L, Duong VT, Shalash AO, et al. Chemical conjugation strategies for the development of protein-based subunit nanovaccines. Vaccines (Basel) 2021; 9(6).
27. Cuccui J, Wren B. Hijacking bacterial glycosylation for the production of glycoconjugates, from vaccines to humanised glycoproteins. J Pharm Pharmacol 2015; 67(3):338-50.
28. Bugya Z, Prechl J, Szénási T, et al. Multiple levels of immunological memory and their association with vaccination. Vaccines (Basel). 2021; 9(2).
29. Anderluh M, Berti F, Bzducha-Wróbel A, et al. Recent advances on smart glycoconjugate vaccines in infections and cancer. Febs j 2022; 289(14):4251-303.
30. Zimmermann P, Ritz N, Perrett KP, et al. Correlation of vaccine responses. Front Immun 2021; 12:646677.
31. Barel LA, Mulard LA. Classical and novel strategies to develop a Shigella glycoconjugate vaccine: from concept to efficacy in human. Human vaccines immunother 2019; 15(6):1338-56.
32. Loughran AJ, Orihuela CJ, Tuomanen EI. Streptococcus pneumoniae: invasion and inflammation. Microbiol Spectr 2019; 7(2).
33. Kay E, Cuccui J, Wren BW. Recent advances in the production of recombinant glycoconjugate vaccines. NPJ Vaccines 2019; 4:16.
34. Choi Y, Han HS, Chong GO, et al. Updates on group B Streptococcus infection in the field of obstetrics and gynecology. Microorganisms 2022; 10(12).
35. Bianchi-Jassir F, Paul P, To KN, et al. Systematic review of Group B Streptococcal capsular types, sequence types and surface proteins as potential vaccine candidates. Vaccine 2020; 38(43):6682-94.
36. Lin SM, Zhi Y, Ahn KB, et al. Status of group B streptococcal vaccine development. Clin Exp Vaccine Res 2018; 7(1):76-81.
37. Adamo R, Nilo A, Castagner B, et al. Synthetically defined glycoprotein vaccines: current status and future directions. Chem Sci 2013; 4(8):2995-3008.
38. Brouwer S, Rivera-Hernandez T, Curren BF, et al. Pathogenesis, epidemiology and control of Group A Streptococcus infection. Nature Rev Microbiol 2023; 21(7):431-47.
39. Chinemerem Nwobodo D, Ugwu MC, Oliseloke Anie C, et al. Antibiotic resistance: The challenges and some emerging strategies for tackling a global menace. J Clin Lab Anal 2022; 36(9):e24655.
40. Tong SY, Davis JS, Eichenberger E, et al. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 2015; 28(3):603-61.
41. Lee AS, de Lencastre H, Garau J, et al. Methicillin-resistant Staphylococcus aureus. Nature Rev Dis Primers 2018; 4(1):18033.
42. Scully IL, Timofeyeva Y, Illenberger A, et al. Performance of a four-antigen Staphylococcus aureus vaccine in preclinical models of invasive S. aureus disease. Microorganisms 2021; 9(1).
43. Pozsgay V, Coxon B, Glaudemans CP, et al. Towards an oligosaccharide-based glycoconjugate vaccine against Shigella dysenteriae type 1. Synlett 2003; 2003(06):0743-67.
44. Khalil IA, Troeger C, Blacker BF, et al. Morbidity and mortality due to Shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990-2016. Lancet Infect Dis 2018; 18(11):1229-40.
45. Perepelov AV, Shekht ME, Liu B, et al. Shigella flexneri O-antigens revisited: final elucidation of the O-acetylation profiles and a survey of the O-antigen structure diversity. FEMS Immunol Med Microbiol 2012; 66(2):201-10.
46. Perepelov AV, L'Vov V L, Liu B, et al. A similarity in the O-acetylation pattern of the O-antigens of Shigella flexneri types 1a, 1b, and 2a. Carbohydr Res 2009; 344(5):687-92.
47. Theillet FX, Simenel C, Guerreiro C, et al. Effects of backbone substitutions on the conformational behavior of Shigella flexneri O-antigens: implications for vaccine strategy. Glycobiology 2011; 21(1):109-21.
48. Phalipon A, Mulard LA, Sansonetti PJ. Vaccination against shigellosis: is it the path that is difficult or is it the difficult that is the path? Microbes Infect 2008; 10(9):1057-62.
49. van der Put RMF, Smitsman C, de Haan A, et al. The first-in-human synthetic glycan-based conjugate vaccine candidate against Shigella. ACS Cent Sci 2022; 8(4):449-60.
50. Han HR, Pak S, 2nd, Guidry A. Prevalence of capsular polysaccharide (CP) types of Staphylococcus aureus isolated from bovine mastitic milk and protection of S. aureus infection in mice with CP vaccine. The Journal of veterinary medical science. 2000;62(12):1331-3.
51. Maira-Litrán T, Kropec A, Goldmann DA, et al. Comparative opsonic and protective activities of Staphylococcus aureus conjugate vaccines containing native or deacetylated Staphylococcal Poly-N-acetyl-beta-(1-6)-glucosamine. Infect Immun 2005; 73(10):6752-62.
52. Mirzaei B, Moosavi SF, Babaei R, et al. Purification and evaluation of polysaccharide intercellular adhesion (pia) antigen from Staphylococcus epidermidis. Curr Microbiol 2016; 73(5):611-7.
53. Mirzaei B, Faridifar P, Shahmoradi M, et al. Genotypic and phenotypic analysis of biofilm formation Staphylococcus epidermidis isolates from clinical specimens. BMC Res Notes. 2020; 13(1):114.
54. França A, Gaio V, Lopes N, et al. Virulence Factors in Coagulase-Negative Staphylococci. Pathogens 2021; 10(2).
55. Gholami SA, Goli HR, Haghshenas MR, et al. Evaluation of polysaccharide intercellular adhesion (PIA) and glycerol teichoic acid (Gly-TA) arisen antibodies to prevention of biofilm formation in Staphylococcus aureus and Staphylococcus epidermidis strains. BMC Res Notes. 2019; 12(1):691.
56. Giguère D. Surface polysaccharides from Acinetobacter baumannii: structures and syntheses. Carbohydr Res 2015; 418:29-43.
57. Mirzaei B, Mousavi SF, Babaei R, et al. Synthesis of conjugated PIA-rSesC and immunological evaluation against biofilm-forming Staphylococcus epidermidis. J Med Microbiol 2019; 68(5):791-802.
58. Mirzaei B, Babaei R, Haghshenas MR, et al. PIA and rSesC mixture arisen antibodies could inhibit the biofilm-formation in Staphylococcus aureus. Rep Biochem Mol Biol 2021; 10(1):1-12.
59. Bahonar S, Ghazvinian M, Haghshenas MR, et al. Purification of PIA and rSesC as putative vaccine candidates against Staphylococcus aureus. Rep Biochem Mol Biol 2019; 8(2):161-7.
60. Kojima Y, Tojo M, Goldmann DA, et al. Antibody to the capsular polysaccharide/adhesin protects rabbits against catheter-related bacteremia due to coagulase-negative staphylococci. J Infect Dis 1990; 162(2):435-41.
61. Takeda S, Pier GB, Kojima Y, et al. Protection against endocarditis due to Staphylococcus epidermidis by immunization with capsular polysaccharide/adhesin. Circulation 1991; 84(6):2539-46.
62. Zarei AE, Almehdar HA, Redwan EM. Hib vaccines: past, present, and future perspectives. J Immun Res 2016; 2016:7203587.
63. Verez-Bencomo V, Fernández-Santana V, Hardy E, et al. A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b. Science. 2004; 305(5683):522-5.
64. Whaley MJ, Vuong JT, Topaz N, et al. Genomic insights on variation underlying capsule expression in meningococcal carriage isolates from university students, United States, 2015-2016. Front Microbiol 2022; 13:815044.
65. Liao G, Zhou Z, Suryawanshi S, et al. Fully synthetic self-adjuvanting α-2,9-oligosialic acid based conjugate vaccines against group c meningitis ACS Cent Sci 2016; 2(4):210-8.
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| Issue | Vol 13 No 2 (2025) | |
| Section | Review Articles | |
| Keywords | ||
| Antibacterial vaccine Conjugate vaccine Glycoconjugate Immuno-genicity Polysaccharide Vaccines. | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Shirmohammadpour M, Mirzaei B. Vaccination against Pathogenic Bacteria: An Insight into Polysaccharide and Conjugate Vaccines. J Med Bacteriol. 2025;13(2):85-107.
