Novel Pneumococcal Serotypes 6C and 6D: Anomaly or Harbinger

Abstract

Clinical use of the 7-valent pneumococcal protein conjugate (PCV7) vaccine, which includes serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, dramatically reduced invasive pneumococcal disease (IPD); however, the effectiveness was diminished due to serotype shift. Although shift due to known serotypes was anticipated, shift by misidentified serotypes was unexpected. We describe the experience with newly recognized serotypes 6C and 6D, which were mistyped as serotypes 6A and 6B, respectively. Although serotype 6D caused only occasional infections, IPD due to serotype 6C disease expanded in the PCV7 era. Subsequent studies showed that PCV7 provided cross-protection against serotype 6A but not serotype 6C. The 13-valent pneumococcal protein conjugate (PCV13) vaccine, which includes PCV7 serotypes plus serotypes 1, 3, 5, 6A, 7F, 19A, may provide protection against IPD due to serotypes 6C and 6D. Regardless, this narrative illustrates the potential impact of unrecognized serotypes on the efficacy of a serotype-specific vaccine.

Immunization with Pneumococcal Surface Protein K of Nonencapsulated Streptococcus pneumoniae Provides Protection in a Mouse Model of Colonization

“…The identification of novel targets for immunization against S. pneumoniae is necessary due to emerging serotypes and increasing numbers of NESp isolates (5,48,49). The unique characteristics of strains of NESp, which seem to have a different surface structure than encapsulated strains based on sequence analysis and recent reports, require vaccine targets that may be specific for NESp (7,15,16).…”

Capsular polysaccharide gene diversity of pneumococcal serotypes 6A, 6B, 6C, and 6D

“…Since the first description of serotype 6C, factor antiserum 6b* (serotype 6A specific) and factor antiserum 6d (serotype 6C specific) have been developed. Serotype 6B and 6D strains are reactive with factor antiserum 6c; however, serotype 6D strains are only reactive with factor antiserum 6d (McEllistrem and Nahm, 2012).…”

“…Serotypes 6C and 6D have increased in prevalence in pneumococcal diseases and have been suggested as recently evolved serotypes (Bratcher et al, 2011;Mavroidi et al, 2004;McEllistrem and Nahm, 2012;Song et al, 2011); therefore, these serotypes were considered to be good candidates for further research in the field of cps gene evolution.…”

“…According to the recent studies exploring capsular genes of serogroup 6 pneumococci (Bratcher et al, 2011;McEllistrem and Nahm, 2012;Song et al, 2011), the capsular operon of serotype 6C was likely generated from unknown resources, and later transferred into pneumococci with many different genomic backgrounds (mostly serotype 6A strains). On the other hand, the capsular gene locus of serotype 6D was likely generated by a recombination event between the capsular loci of serotypes 6B and 6C and was later also inserted into strains from other serotypes, such as 6A and 6B.…”

Baseline Epidemiology and Genetic Structure of Streptococcus pneumoniae Serotype 6D in Southern Israel Prior to Introduction of Pneumococcal Conjugate Vaccines

“…Preliminary in vitro data suggest that the S. pneumoniae serotype 6B component of these vaccines elicits antibodies that are cross-opsonic to S. pneumoniae serotype 6D (12). However, clinical data are not yet available to confirm these findings.…”