Project name: Streptococcus pneumoniae

Description: Implementation of conjugate technology revolutionized the ability to effectively elicit long-lasting immune responses to bacterial capsular polysaccharides, and significantly reduced the burden of invasive pneumococcal disease caused by vaccine serotypes since conjugate vaccine introduction in 2000. While expansion of conjugate vaccine serotype coverage is designed to target residual disease burden to pneumococcal serotypes not contained in earlier vaccine versions, details of polysaccharide antigen structure, heterogeneity, and epitope structure components contributing to vaccine-mediated immunity are not always clear. Analysis of Streptococcus pneumoniae serotype 12F polysaccharide by two-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry revealed a partial substitution of N-acetyl-galactosamine by the keto sugar 2-acetamido-2,6-dideoxy-xylo-hexos-4-ulose (Sug) in up to 25% of the repeat units. This substitution was not described in any previous published structures for 12F (Leontein et al. 1981. Can J Chem 59: 2081-2085). Screening a series of contemporary 12F clinical isolates (n=17) identified Sug incorporation at varying levels in all strains examined. Thus, partial Sug substitution in S. pneumoniae serotype 12F may have always been present but is now detectable by state-of-the-art analytical techniques. During the steps of conjugation, the serotype 12F Sug epitope is modified by reduction, and both polysaccharide PPSV23 and conjugate PCV20 vaccines contain 12F antigens with little-to-no Sug epitope. Both PCV20 and PPSV23 vaccines were evaluated for protection against circulating 12F strains with varying amounts of Sug in their repeat unit based on an opsonophagocytic killing assay. Both vaccines elicited neutralizing antibodies against serotype 12F, independent of Sug level between ~2 to 25 mol%. These findings suggest that the newly identified serotype 12F Sug epitope is likely not an essential epitope for vaccine-elicited protection.

Data type: raw sequence reads

Sample scope: Monoisolate

Relevance: Medical

Last updated: 2023-01-25