Polysaccharide Capsule Composition of Pneumococcal Serotype 19A Subtypes Is Unaltered among Subtypes and Independent of the Nutritional Environment

Abstract

ABSTRACT Serotype 19A strains have emerged as a cause of invasive pneumococcal disease after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), and serotype 19A has now been included in the recent 13-valent vaccine (PCV13). Genetic analysis has revealed at least three different capsular serotype 19A subtypes, and nutritional environment-dependent variation of the 19A capsule structure has been reported. Pneumococcal vaccine effectiveness and serotyping accuracy might be impaired by structural differences in serotype 19A capsules. We therefore analyzed the distribution of 19A subtypes collected within a Swiss national surveillance program and determined capsule composition under different nutritional conditions with high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy. After the introduction of PCV7, a significant relative increase of subtype 19A-II and decrease of 19A-I occurred. Chemical analyses showed no difference in the composition as well as the linkage of 19A subtype capsular saccharides grown in defined and undefined growth media, which is consistent with a trisaccharide repeat unit composed of rhamnose, N -acetyl-mannosamine, and glucose. In summary, our study suggests that no structural variance dependent of the nutritional environment or the subtype exists. The serotype 19A subtype shift observed after the introduction of the PCV7 can therefore not be explained by selection of a capsule structure variant. However, capsule composition analysis of emerging 19A clones is recommended in cases where there is no other explanation for a selective advantage, such as antibiotic resistance or loss or acquisition of other virulence factors.