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Chapter 11 : Conjugation Chemistry
Authors:
Andrew Lees1,
Velupillai Puvanesarajah2,
Carl E. Frasch3
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Affiliations:
1: Fina BioSolutions LLC, 9610 Medical Center Dr., Suite 200, Rockville, MD 20850;
2: Sanofi-Aventis, Swiftwater, PA 18370;
3: Frasch Biologics Consulting, P.O. Box 986, Martinsburg, WV 25402
Content Type: Monograph
Publication Year:
2008
Category: Bacterial Pathogenesis; Immunology
Book DOI:
10.1128/9781555815820
Chapter DOI:
10.1128/9781555815820.ch11
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Conjugation Chemistry, Page 1 of 2
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Abstract:
Most bacteria that cause invasive disease, especially those that cause bacteremia, are protected from innate host immunity because they express polysaccharides (PSs) on their cell surfaces. The bacterial capsular PSs are composed of thousands of carbohydrate repeat units resulting in polydisperse polymers that can have molecular masses into the millions of daltons. Multivalent pneumococcal conjugate vaccines present additional complexities with regard to their syntheses, as each serotype is chemically distinct, effectively requiring the optimization of the manufacture of seven or more individual vaccines. Various proteins and peptide molecules have been demonstrated, in preclinical studies, to be effective carriers for PSs and oligosaccharides, but only a small number of protein carriers have been investigated in humans. Surface-exposed proteins and toxins from human pathogenic bacteria have been used as carriers, as they contain one or more of the T-cell epitopes. In order to convert PSs into T-cell-dependent antigens, the protein must be chemically linked to the carbohydrate; that is, there must be covalent links between the two components. Protein solubility at the required pH, concentration, and temperature is an important determinant of the suitability of a protein for use in a particular conjugation scheme. The conjugation step is generally the slowest chemical step and risks damage to the components. Efforts should be made to improve conjugation efficiencies to levels at which the residual unconjugated components, especially free PSs, do not interfere with inductions of protective immune responses. The use of efficient, mild conjugation chemistry would allow for higher yields of vaccine.
Citation:
Lees A, Puvanesarajah V, Frasch C.
2008.
Conjugation Chemistry,
p 163-174.
In
Siber G, Klugman K, Mäkelä P (ed),
Pneumococcal Vaccines.
ASM Press, Washington, DC.
doi: 10.1128/9781555815820.ch11
Key Concept Ranking
- Pneumococcal Conjugate Vaccine
- 0.5836534
- Meningococcal Conjugate Vaccine
- 0.5687945
- Outer Membrane Proteins
- 0.4636095
0.5836534
Figures
Conjugation Chemistry
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Citation:
Lees A, Puvanesarajah V, Frasch C.
2008.
Conjugation Chemistry,
p 163-174.
In
Siber G, Klugman K, Mäkelä P (ed),
Pneumococcal Vaccines.
ASM Press, Washington, DC.
doi: 10.1128/9781555815820.ch11
/content/10.1128/9781555815820.ch11.ch11fig01
Figure 1
General overview of the protein (Pr)-PS conjugation process.
10.1128/9781555815820/f0166-01_thmb.gif
10.1128/9781555815820/f0166-01.gif
Figure 1
General overview of the protein (Pr)-PS conjugation process.
Citation:
Lees A, Puvanesarajah V, Frasch C.
2008.
Conjugation Chemistry,
p 163-174.
In
Siber G, Klugman K, Mäkelä P (ed),
Pneumococcal Vaccines.
ASM Press, Washington, DC.
doi: 10.1128/9781555815820.ch11
/content/10.1128/9781555815820.ch11.ch11fig02
Figure 2
Reaction schemes for reductive amination (A) and cyanylation (B) using CDAP. Prot, protein.
10.1128/9781555815820/f0169-01_thmb.gif
10.1128/9781555815820/f0169-01.gif
Figure 2
Reaction schemes for reductive amination (A) and cyanylation (B) using CDAP. Prot, protein.
Citation:
Lees A, Puvanesarajah V, Frasch C.
2008.
Conjugation Chemistry,
p 163-174.
In
Siber G, Klugman K, Mäkelä P (ed),
Pneumococcal Vaccines.
ASM Press, Washington, DC.
doi: 10.1128/9781555815820.ch11
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Tables
Conjugation Chemistry
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Citation:
Lees A, Puvanesarajah V, Frasch C.
2008.
Conjugation Chemistry,
p 163-174.
In
Siber G, Klugman K, Mäkelä P (ed),
Pneumococcal Vaccines.
ASM Press, Washington, DC.
doi: 10.1128/9781555815820.ch11
/content/10.1128/9781555815820.ch11.ch11tab01
Table 1
Comparison of conjugation methods that have been used for PCV
Table 1
Comparison of conjugation methods that have been used for PCV
Citation:
Lees A, Puvanesarajah V, Frasch C.
2008.
Conjugation Chemistry,
p 163-174.
In
Siber G, Klugman K, Mäkelä P (ed),
Pneumococcal Vaccines.
ASM Press, Washington, DC.
doi: 10.1128/9781555815820.ch11