Impact and Control of Sugar Size in Glycoconjugate Vaccines
Abstract
:1. Introduction
2. Role of Sugar Length on the Immunogenicity of Glycoconjugate Vaccines
2.1. Dextrans
2.2. Group B Streptococcus
2.3. Streptococcus pneumoniae
2.4. Neisseria meningitidis
2.5. Salmonella typhi
2.6. Salmonella typhimurium
2.7. Francisella tularensis
2.8. Shigella
2.9. Vibrio cholerae
2.10. Haemophilus influenzae Type B
3. Methods to Reduce Polysaccharide Size
3.1. Hydrolysis
3.2. Mild Acidic Hydrolysis
3.2.1. Neisseria meningitidis
3.2.2. Hemophilus influenzae Type B
3.2.3. Streptococcus pneumoniae
3.3. Thermal Hydrolysis
3.3.1. Hemophilus influenzae Type B
3.4. Reactive Oxygen and Nitrogen Species
3.5. Hydrogen Peroxide
3.5.1. Neisseria meningitidis
3.5.2. Salmonella typhi
3.6. Ozone
3.6.1. Group B Streptococcus
3.7. Nitric Oxide and Nitrous Acid
3.7.1. Group B Streptococcus
3.7.2. Streptococcus pneumoniae
3.8. Periodate Oxidation
3.8.1. Neisseria meningitidis
3.8.2. Hemophilus influenzae Type B
3.8.3. Streptococcus pneumoniae
3.9. Enzymatic Hydrolysis
3.9.1. Group B Streptococcus
3.9.2. Salmonella typhimurium
3.9.3. Klebsiella pneumoniae
3.9.4. Hemophilus influenzae Type b
3.10. Homogenization
3.11. Sonication
4. Bioconjugate Vaccines and New Ways to Modulate PS Length
5. Oligosaccharides from Monomers through Synthetic Approaches
6. Discussion
Terminology and Abbreviations
BSA | Bovine serum albumin |
CPS | Capsular polysaccharide(s) |
CRM197 | Cross-Reactive Material 197 |
Dx | Dextran(s) |
DT | Diphtheria Toxoid |
GBS | Group B Streptococcus |
Hib | Hemophilus influenzae type b |
Men | Meningococcus |
MW | Molecular weight |
O-SP | O-specific polysaccharide |
OS | Oligosaccharide(s). This term will be used in this paper to indicate a saccharide fragment smaller than the native polysaccharide |
PRP | Polyribosylribitol Phosphate |
PS | Polysaccharide(s) |
RU | Repeating unit(s) |
TT | Tetanus toxoid |
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Method | Target | Properties | Examples * | References |
---|---|---|---|---|
Hydrolysis | Glycosidic O atom | Simple, scalable, and reproducible. Particularly useful when not all glycosidic linkages are cleaved at the same rate for homopolymers. It may impact the structural integrity of the RU. | Men CPS (A, C, W-135, Y, X), Hib CPS, S. pneumoniae CPS (3, 6A) (temperature-aided acid hydrolysis), Hib CPS (thermal hydrolysis) | [12,16,20,33,37,45,54,57,58,59,60,61,62,63,64,65,66] |
Reactive oxygen and nitrogen species | C–H of Carbons involved in glycosidic bond (hydrogen peroxide) Anomeric Carbon (ozone) Amino or Sulfo-amino groups (nitrosonium cation) | Simple, scalable, and reproducible. Ozone targets mainly PS β-d-linkages whereas nitrosation requires a free amino or sulfo-amino group. Depending on the specific structure, this may or may not result in fragmentation. | Men CPS (A, C, W-135, Y), S. Typhi Vi CPS (hydrogen peroxide), GBS CPS (ozone), GBS CPS (II and III), S. pneumoniae CPS (14) (nitrosonium cation) | [26,31,41,42,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83] |
Periodate oxidation | Vicinal diols | Simple, scalable, and reproducible. Selectivity can be controlled by adjusting the oxidant concentration. It requires vicinal diols in specific positions (e.g., MenC CPS or Hib CPS) to lead to fragmentation, so this method cannot be generally applicable. | MenC CPS, Hib CPS, S. pneumoniae CPS (4) | [27,53,84,85,86,87,88,89,90,91] |
Enzymatic hydrolysis | O-glycosidic linkages | Recommended for PS containing labile moieties (e.g., sialic acid side chains) as this only targets the enzyme-specific glycosidic linkage. Enzymes only hydrolyze specific substrates and may preferentially hydrolyze smaller saccharides. | GBS III CPS, Klebsiella pneumoniae CPS (K1 and K2), S. Typhimurium O-SP, Hib CPS | [23,24,26,43,54,92,93,94] |
Homogenization | Mechanical sizing | Simple and scalable. Very reproducible and with no side reactions. Pressures needed to create very small OS may not be achievable. | S. pneumoniae CPS, Men CPS, GBS CPS, Staphylococcus aureus CPS | [20] |
Sonication | Physical shearing of the PS via ultrasonic waves | Simple, but not easily scalable or reproducible. Generally, it does not induce side reactions, but the sonication probe may degrade and introduce metal contaminants into the PS solution. | S. pneumoniae CPS, S. Typhi Vi CPS, Hib CPS, Staphylococcus aureus CPS (5 and 8), Cryptococcus neoformans GXM CPS(A) | [20,38,95,96,97,98,99] |
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Stefanetti, G.; MacLennan, C.A.; Micoli, F. Impact and Control of Sugar Size in Glycoconjugate Vaccines. Molecules 2022, 27, 6432. https://doi.org/10.3390/molecules27196432
Stefanetti G, MacLennan CA, Micoli F. Impact and Control of Sugar Size in Glycoconjugate Vaccines. Molecules. 2022; 27(19):6432. https://doi.org/10.3390/molecules27196432
Chicago/Turabian StyleStefanetti, Giuseppe, Calman Alexander MacLennan, and Francesca Micoli. 2022. "Impact and Control of Sugar Size in Glycoconjugate Vaccines" Molecules 27, no. 19: 6432. https://doi.org/10.3390/molecules27196432