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.

Carbohydrate Research
|February 7, 2015
PubMed

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.

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