Background Because classical pneumococcal serotyping cannot distinguish between serotypes 6A and 6C, the effects of pneumococcal vaccines against serotype 6C are unknown. Pneumococcal vaccines contain 6B, but do not contain 6A and 6C. Methods We used a phagocytic killing assay to estimate the immunogenicity of 7-valent conjugate vaccine (PCV7) in children and 23-valent polysaccharide vaccine (PPV23) in adults against serotypes 6A and 6C. We evaluated trends in invasive pneumococcal disease (IPD) caused by serotypes 6A and 6C using active surveillance in the U.S. Results Sera from PCV7-immunized children had median opsonization indices of 150 and <20 for serotypes 6A and 6C, respectively. Similarly, only 52% (25/48) of adults vaccinated with PPV23 showed opsonic indices greater than 20 against serotype 6C. During 1999–2006, the incidence (cases per 100,000) of serotype 6A IPD declined from 4.9 to 0.46 (−91%, P<0.05) among children aged <5 years, and from 0.86 to 0.36 (−58%, P<0.05) among persons aged ≥5 years. Although incidence of 6C IPD showed no consistent trend (range 0–0.6) among <5 year-olds, it increased from 0.25 to 0.62 (P<0.05) among persons aged ≥5 years. Conclusions PCV7 introduction has led to reductions in serotype 6A IPD, but not serotype 6C IPD in the U.S.

A new pneumococcal serotype within serogroup 6, 6C, was recently discovered during the development of a monoclonal antibody (MAb)-based typing scheme (7,14), when a subset of conventionally serotyped 6A isolates (CS6As) did not bind to one of the two 6A-specific MAbs used. Subsequent analysis of this CS6A subset revealed a different capsular structure, which was designated 6C (14). The serotype 6C capsular biosynthetic locus (cps) appears to be derived from replacement of the wciN gene at the 6A cps locus with a divergent 6C-specific counterpart that encodes a different glycosyl transferase, resulting in a sugar substitution in the polysaccharide repeating unit (13).The MAb typing system was used to resolve serotype 6C isolates among CS6As recovered during the pre-pneumococcal 7-valent conjugate vaccine (PCV7) year 1999 and post-PCV7 years 2003 to 2006 from areas under continuous surveillance in Active Bacterial Core surveillance (ABCs) in the United States (10). This investigation revealed a marked decrease in the rate of serotype 6A invasive pneumococcal disease (IPD) in the post-PCV7 period that was apparently due to cross-protection mediated by the serotype 6B component included in PCV7.The investigation also revealed a small, yet significant, increase in the rate of serotype 6C IPD. Here, we describe an expedient PCR assay for resolution of serotype 6C and true serotype 6A from CS6As. We extend our recent observations (10)

Serogroup 6 of Streptococcus pneumoniae contains three serotypes named 6A, 6B and 6C with highly homologous capsule gene loci. The 6A and 6B capsule gene loci consistently differ from each other by only one nucleotide in the wciP gene. The 6A capsule gene locus has a galactosyl transferase, which has been replaced with a glucosyl transferase in the 6C capsule gene locus. We considered that a new serotype named “6X1” would be possible if the galactosyl transferase of the 6B capsule gene locus is replaced with the glucosyl transferase of 6C. We demonstrate that this gene transfer yields a viable pneumococcal strain and the capsular polysaccharide from this strain has the predicted chemical structure and serologic similarity to the capsular polysaccharide of the 6B serotype. The new strain (i.e., serotype 6X1) is typed as 6B by the quellung reaction but it can be distinguished from 6B strains with monoclonal antibodies to 6B polysaccharide. Reexamination of 264 pneumococcal isolates that were previously typed as 6B with classical typing methods revealed no isolates expressing serotype 6X1. Nevertheless, this study shows this capsular polysaccharide is biochemically possible and could exist/emerge in nature.

Objectives We have recently found a high prevalence of non-typeable pneumococcal isolates (NTPn) circulating in day-care centers in Central Brazil, besides serotype 14 isolates. We therefore examined the genetic relationship among NTPn and serotype 14 from carriage and invasive pneumococcal isolates obtained from children attending emergency rooms enrolled in a population-based surveillance. Methods The isolates were characterized by Quellung reaction serotyping, PCR for the presence of pneumolysin and the loci for a capsule gene (cpsA) and the type 14 gene (cps14H) in all NTPn, and by multilocus sequence typing and pulsed field gel electrophoresis. Results 87.2% of the isolates were clustered into nine clusters. The major cluster included 41 pneumococcal serotype 14 (28 carriage and 13 invasive isolates) and two NTPn related to the global pneumococcal clone Spain 9V-3. Overall, 95.4% of the NTPn carriage strains were genetically related to carriage or invasive strains expressing serotype 14. A dominant NTPn lineage was found, that grouped 14 pneumococcal strains. Almost half of the multidrug-resistant isolates grouped into the NTPn cluster. Conclusion These findings provide baseline data to assess the impact of the pneumococcal vaccination on the molecular epidemiology of S. pneumoniae. Changes in frequency of NTPn isolates and also genetic changes should be carefully monitored post vaccination, to detect potential vaccine-escape or replacement disease by capsule switched strains, especially in areas where colonization with NTPn has been frequently observed.