Carriers and Antigens: New Developments in Glycoconjugate Vaccines

doi:10.3390/vaccines11020219

Review

. 2023 Jan 19;11(2):219.

doi: 10.3390/vaccines11020219.

Carriers and Antigens: New Developments in Glycoconjugate Vaccines

Robert M F van der Put^{1

2}, Bernard Metz¹, Roland J Pieters²

Affiliations

¹ Intravacc, P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
² Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.

PMID: 36851097
PMCID: PMC9962112
DOI: 10.3390/vaccines11020219

Review

Carriers and Antigens: New Developments in Glycoconjugate Vaccines

Robert M F van der Put et al. Vaccines (Basel). 2023.

. 2023 Jan 19;11(2):219.

doi: 10.3390/vaccines11020219.

Authors

Robert M F van der Put^{1

2}, Bernard Metz¹, Roland J Pieters²

Affiliations

¹ Intravacc, P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
² Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.

PMID: 36851097
PMCID: PMC9962112
DOI: 10.3390/vaccines11020219

Abstract

Glycoconjugate vaccines have proven their worth in the protection and prevention of infectious diseases. The introduction of the Haemophilus influenzae type b vaccine is the prime example, followed by other glycoconjugate vaccines. Glycoconjugate vaccines consist of two components: the carrier protein and the carbohydrate antigen. Current carrier proteins are tetanus toxoid, diphtheria toxoid, CRM197, Haemophilus protein D and the outer membrane protein complex of serogroup B meningococcus. Carbohydrate antigens have been produced mainly by extraction and purification from the original host. However, current efforts show great advances in the development of synthetically produced oligosaccharides and bioconjugation. This review evaluates the advances of glycoconjugate vaccines in the last five years. We focus on developments regarding both new carriers and antigens. Innovative developments regarding carriers are outer membrane vesicles, glycoengineered proteins, new carrier proteins, virus-like particles, protein nanocages and peptides. With regard to conjugated antigens, we describe recent developments in the field of antimicrobial resistance (AMR) and ESKAPE pathogens.

Keywords: ESKAPE pathogens; antimicrobial resistance; carbohydrates; carrier proteins; glycoconjugate vaccines; glycoengineered proteins; outer membrane vesicles; protein nanocages; virus-like particles.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
New carrier proteins for conjugate vaccines; OMV and GMMA (1), glycoengineered proteins (**2^a** *P. aeruginosa* exotoxin A, PDB 1IKQ) and OMV (**2^b**), proteins (**3^a** *Streptococcus pyogenes* streptolysin O, PDB 4HSC and **3^b** receptor-binding fragment HC of tetanus neurotoxin, PDB 1AF9), VLP (4), protein nanocages (5) and peptides (6).

**Figure 2**
Priority list scaling for the ESKAPE pathogens according to both CDC and WHO.

**Figure 3**
EARC nr. of deaths caused by ESKAPE pathogens in 2019 [138].

**Figure 4**
ESKAPE pathogens and examples of target antigens: *E. feacium*: cell wall teichoic acid [141]; *S. aureus*: trisaccharide type 8 capsular polysaccharide [142]; *K. pneumoniae*: capsular polysaccharide K2 [143]; *A. baumanii*: pseudaminic-acid [144]; *P. aeruginosa*: methyl rhamnan pentasaccharide [145]; *E. coli*: serotype O25B [146].

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References

1. CDC History of Smallpox. [(accessed on 29 September 2022)]; Available online: https://www.cdc.gov/smallpox/history/history.html.
1. Avery O.T., Goebel W.F. Chemo-Immunological Studies on Conjugated Carbohydrate-Proteins: Ii. Immunological Specificity of Synthetic Sugar-Protein Antigens. J. Exp. Med. 1929;50:533–550. doi: 10.1084/jem.50.4.533. - DOI - PMC - PubMed
1. Schneerson R., Robbins J.B., Parke J.C., Jr., Bell C., Schlesselman J.J., Sutton A., Wang Z., Schiffman G., Karpas A., Shiloach J. Quantitative and qualitative analyses of serum antibodies elicited in adults by Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-tetanus toxoid conjugates. Infect. Immun. 1986;52:519–528. doi: 10.1128/iai.52.2.519-528.1986. - DOI - PMC - PubMed
1. Schneerson R., Robbins J.B., Barrera O., Sutton A., Habig W.B., Hardegree M.C., Chaimovich J. Haemophilus influenzae type B polysaccharide-protein conjugates: Model for a new generation of capsular polysaccharide vaccines. Prog. Clin. Biol. Res. 1980;47:77–94. - PubMed
1. Pollard A.J., Perrett K.P., Beverley P.C. Maintaining protection against invasive bacteria with protein-polysaccharide conjugate vaccines. Nat. Rev. Immunol. 2009;9:213–220. doi: 10.1038/nri2494. - DOI - PubMed

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[1] CDC History of Smallpox. [(accessed on 29 September 2022)]; Available online: https://www.cdc.gov/smallpox/history/history.html.

[2] CDC History of Smallpox. [(accessed on 29 September 2022)]; Available online: https://www.cdc.gov/smallpox/history/history.html.

[3] Avery O.T., Goebel W.F. Chemo-Immunological Studies on Conjugated Carbohydrate-Proteins: Ii. Immunological Specificity of Synthetic Sugar-Protein Antigens. J. Exp. Med. 1929;50:533–550. doi: 10.1084/jem.50.4.533. - DOI - PMC - PubMed

[4] Avery O.T., Goebel W.F. Chemo-Immunological Studies on Conjugated Carbohydrate-Proteins: Ii. Immunological Specificity of Synthetic Sugar-Protein Antigens. J. Exp. Med. 1929;50:533–550. doi: 10.1084/jem.50.4.533. - DOI - PMC - PubMed

[5] Schneerson R., Robbins J.B., Parke J.C., Jr., Bell C., Schlesselman J.J., Sutton A., Wang Z., Schiffman G., Karpas A., Shiloach J. Quantitative and qualitative analyses of serum antibodies elicited in adults by Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-tetanus toxoid conjugates. Infect. Immun. 1986;52:519–528. doi: 10.1128/iai.52.2.519-528.1986. - DOI - PMC - PubMed

[6] Schneerson R., Robbins J.B., Parke J.C., Jr., Bell C., Schlesselman J.J., Sutton A., Wang Z., Schiffman G., Karpas A., Shiloach J. Quantitative and qualitative analyses of serum antibodies elicited in adults by Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-tetanus toxoid conjugates. Infect. Immun. 1986;52:519–528. doi: 10.1128/iai.52.2.519-528.1986. - DOI - PMC - PubMed

[7] Schneerson R., Robbins J.B., Barrera O., Sutton A., Habig W.B., Hardegree M.C., Chaimovich J. Haemophilus influenzae type B polysaccharide-protein conjugates: Model for a new generation of capsular polysaccharide vaccines. Prog. Clin. Biol. Res. 1980;47:77–94. - PubMed

[8] Schneerson R., Robbins J.B., Barrera O., Sutton A., Habig W.B., Hardegree M.C., Chaimovich J. Haemophilus influenzae type B polysaccharide-protein conjugates: Model for a new generation of capsular polysaccharide vaccines. Prog. Clin. Biol. Res. 1980;47:77–94. - PubMed

[9] Pollard A.J., Perrett K.P., Beverley P.C. Maintaining protection against invasive bacteria with protein-polysaccharide conjugate vaccines. Nat. Rev. Immunol. 2009;9:213–220. doi: 10.1038/nri2494. - DOI - PubMed

[10] Pollard A.J., Perrett K.P., Beverley P.C. Maintaining protection against invasive bacteria with protein-polysaccharide conjugate vaccines. Nat. Rev. Immunol. 2009;9:213–220. doi: 10.1038/nri2494. - DOI - PubMed

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Carriers and Antigens: New Developments in Glycoconjugate Vaccines

Affiliations

Carriers and Antigens: New Developments in Glycoconjugate Vaccines

Authors

Affiliations

Abstract

Conflict of interest statement

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