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Review
. 2023 Feb 10;9(2):178-212.
doi: 10.1021/acsinfecdis.2c00559. Epub 2023 Jan 27.

Development in the Concept of Bacterial Polysaccharide Repeating Unit-Based Antibacterial Conjugate Vaccines

Affiliations
Review

Development in the Concept of Bacterial Polysaccharide Repeating Unit-Based Antibacterial Conjugate Vaccines

Rajendra Rohokale et al. ACS Infect Dis. .

Abstract

The surface of cells is coated with a dense layer of glycans, known as the cell glycocalyx. The complex glycans in the glycocalyx are involved in various biological events, such as bacterial pathogenesis, protection of bacteria from environmental stresses, etc. Polysaccharides on the bacterial cell surface are highly conserved and accessible molecules, and thus they are excellent immunological targets. Consequently, bacterial polysaccharides and their repeating units have been extensively studied as antigens for the development of antibacterial vaccines. This Review surveys the recent developments in the synthetic and immunological investigations of bacterial polysaccharide repeating unit-based conjugate vaccines against several human pathogenic bacteria. The major challenges associated with the development of functional carbohydrate-based antibacterial conjugate vaccines are also considered.

Keywords: Antibacterial Vaccine; Conjugate Vaccine; Glycoconjugate; Immunogenicity; Oligosaccharide; Polysaccharide.

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Figures

Figure 1:
Figure 1:
Major milestones in the history of carbohydrate-based antibacterial vaccine development.
Figure 2.
Figure 2.
Three major classes of glycconjugate vaccines. (a) The traditional polysaccharide-based glycoconjugate vaccines; (b) semi-synthetic glycoconjugate vaccines consisting of synthetic, strcuturally well-defined oligosaccharide antigens; (c) structurally defined fully synthetic glycoconjugate vaccines consisting of synthetic oligosaccharide antigens and synthetic carrier molecules.
Figure 3.
Figure 3.
The general immunology of carbohydrate-based antibacterial vaccines in human.
Figure 4.
Figure 4.
Structures of commercialized semi-synthetic glycoconjugate Hib vaccine Quimi-Hib 1 (a) and semi-synthetic glycoconjugates 25 explored as Hib vaccines by the Seeberger group (b).
Figure 5.
Figure 5.
Structures of MenA CPS and its synthetic 1-C-phosphono and carbocyclic analogues, as well as their protein conjugates explored as MenA vaccines.
Figure 6.
Figure 6.
Structures of MenC CPS, its synthetic oligosaccharides 15-20, and the protein conjugates 21-28 of oligosaccharides 15-20.
Figure 7.
Figure 7.
Structures of MenW CPS, its synthetic oligosaccharides 29-33a, and the CRM197 conjugates 29-33b of oligosaccharides 29-33a.
Figure 8.
Figure 8.
Structures of the MenX CPS and protein conjugates 34–36 of MenX CPS oligosaccharides.
Figure 9.
Figure 9.
Structures of the repeating units of A. baumannii EPSs and their protein glycoconjugates.
Figure 10.
Figure 10.
Structures of the synthetic oligosaccharide-protein conjugates 42-50 as vaccine candidates for S. pneumoniae serotypes ST1, ST2, ST3, ST5, ST8, ST6B, ST14, ST19A-F, and ST23F.
Figure 11.
Figure 11.
Structures of synthetic conjugate vaccines 5153 for S. flexneri 2a made of oligosaccharides of its O-antigen and 54 made of S. flexneri 2a O-antigen oligosaccharides with nonstoichiometric O-acetylation, as well as glycoconjugate vaccines 55–58 for S. dysenteriae type-1.
Figure 12.
Figure 12.
Structures of synthetic glycoconjugates 59, 60a-d, and 61 explored as anti-anthrax vaccines
Figure. 13
Figure. 13
Structures of the surface polysaccharides of C. difficile PS-I, PS-II, and PS-III 6264 (a), synthetic glycoconjugates 6567 consisting of PS-II oligosaccharides (b), and native polysaccharide PS-II-CRM197 glycoconjugate 68 (c) investigated as vaccines for C. difficile.
Figure 14.
Figure 14.
Structures of Brucella O-antigen and its synthetic oligosaccharide analogs 69-75a, as well as their protein conjugates 69-75b.
Figure 15.
Figure 15.
Structures of the type I O-PS 76a and 76b of B. pseudomallei and B. mallei and the protein conjugates 77a-b, 78a-b, 79, 80a-f, and 81a-f of B. pseudomallei and B. mallei CPS oligosaccharides.
Figure 16.
Figure 16.
Structures of the O-antigens 82a and 82b of Vibrio cholerae O1 Inaba and Ogawa serotypes, respectively, the BSA-Ogawa serotype oligosaccharide conjugates 83a-c, and rEPA-Inaba and Ogawa serotype oligosaccharide 84-87a,b, as well as structures of the V. cholerae O139 O-antigen 88 and its protein conjugates 99a-c.
Figure 17.
Figure 17.
Structures of mycobacterial LAMs and related molecules (a) and the KLH conjugates 90a-f of synthetic PIM derivatives (b).
Figure 18.
Figure 18.
Structures of KLH and BSA glycoconjugates 91-93a and 91-93b of the synthetic LAM oligosaccharides and MPLA conjugates 94 and 95 of LAM tetrasaccharide
Figure 19:
Figure 19:
LAM-related arabinofuranosyl oligosaccharides conjugates 96a-h and 97a-c studied as TB diagnostic agents.
Figure 20.
Figure 20.
Structures of the conserved GAS cell wall polysaccharide 101 and GAS oligosaccharide–protein conjugates 102-108 investigated as anti-GAS vaccines.
Figure 21.
Figure 21.
Structures of the conserved CPSs on the cell surface of GBS serotypes Ia, Ib, II, III, IV, V, VI, VII, VIII, and IX.
Figure 22.
Figure 22.
Structure of serotype III GBS oligosaccharide-CRM197 conjugates 116-119 and serotype Ia GBS oligosaccharide-protein conjugates 120a-d.
Figure 23.
Figure 23.
Structures of the protein conjugates of oligosaccharide epitopes of a group-specific cell surface polysaccharide shared by different GBS serotypes.

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