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Updated: Apr 17, 2026

Capsular Serotyping of Streptococcus pneumoniae Using the Quellung Reaction
Published on: February 24, 2014
Capsular polysaccharide conformations in pneumococcal serotypes 19F and 19A
Michelle M Kuttel1, Graham E Jackson2, Mpho Mafata2
1Department of Computer Science, University of Cape Town, Cape Town, South Africa.
Insights
Pneumococcal conjugate vaccines (PCV) have reduced disease, but serotype 19A infections increased. Structural differences between 19F and 19A polysaccharides explain the lack of cross-protection, guiding future vaccine development.
Area of Science:
- Microbiology
- Immunology
- Structural Biology
Background:
- Streptococcus pneumoniae causes significant childhood illness.
- Pneumococcal conjugate vaccines (PCV7) reduced disease but increased non-vaccine serotype 19A infections.
- Cross-protection from vaccine serotype 19F to 19A was expected but not observed.
Purpose of the Study:
- To investigate the structural basis for the lack of cross-protection between Streptococcus pneumoniae serotypes 19F and 19A.
- To compare the conformational properties of 19F and 19A oligosaccharide chains.
Main Methods:
- Solution simulations of 19F and 19A oligosaccharide chains.
- Nuclear Magnetic Resonance (NMR) NOESY experiments to determine inter-residue distances.
Main Results:
- Both 19F and 19A polysaccharides form unstructured random coils.
- Distinct conformational differences were identified: 19F has residues in near-orthogonal orientations, while 19A has residues in similar orientations.
- 19F favors extended conformations, whereas 19A shows a high prevalence of tight hairpin bends.
Conclusions:
- Conformational differences between 19F and 19A polysaccharides likely explain the absence of antibody cross-protection.
- These findings are crucial for understanding pneumococcal serotype epidemiology and for designing next-generation pneumococcal vaccines like PCV13.
Abstract:
Streptococcus pneumoniae is a significant pathogen in children. Although the PCV7 pneumococcal conjugate vaccine has reduced pneumococcal disease, non-vaccine serotype 19A infection has increased, despite expectations of cross-protection from vaccine serotype 19F. Serotype 19A is included in the new PCV13 vaccine, but not in PCV10. In the solution simulations of 19F and 19A oligosaccharide chains reported here, both polysaccharides form unstructured random coils, with inflexible repeat units linked by mobile phosphodiester linkages. However, there are clear conformational differences. In the 19F repeat unit, the rhamnose residue is nearly orthogonal to the other residues, whereas 19A has residues in similar orientations. This finding is corroborated by key inter-residue distances calculated from NMR NOESY experiments. Further, 19F is predominantly in extended conformations, whereas 19A exhibits a high prevalence of tight hairpin bends. These conformational differences may account for a lack of antibody cross-protection between serotypes 19F and 19A.
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