Biochemical and Immunological Insights into Capsular Polysaccharide of <i>Streptococcus pneumoniae</i> Serotype 38 (American Type 71)─An Emerging Nonvaccine Serotype

Invasive pneumococcal disease presents a threat to humankind, predominantly affecting children and the elderly. Despite the availability of high-valency pneumococcal polysaccharide vaccine of PPSV23 (PNEUMOVAX 23) and conjugate vaccines such as VAXNEUVANCE and PREVNAR 20, nonvaccine serotypes continue to contribute to higher mortality rates. The characterization of nonvaccine serotypes is becoming increasingly crucial considering an increase in their prevalence. In this study, biochemical characteristics, immunological properties, and critical quality attributes of the capsular polysaccharide isolated from prevalent nonvaccine serotype 38 (American type 71) have been examined. Advanced analytical techniques, including multiangle light scattering (MALS), ion chromatography, and dynamic light scattering in addition to conventional biochemical methods and SLOTBLOT analysis, were employed. We observed that serotype 38 capsular polysaccharide has a molar mass of 768 kDa with a distribution of 1.5 (±4.5%) and a <i>z</i>-average radius of gyration (<i>R</i> _g) of 90 nm. The polysaccharide composition included galactose, <i>N</i>-acetylglucosamine, and galacturonic acid, with a distinct peak indicating the presence of the amino acid serine. The near-zero zeta potential measurements indicated that the polysaccharide is either zwitterionic or uncharged. Serotype 38 polysaccharide exhibited immunological cross-reactivity with serotype 5 and serotype 1 polyclonal sera, likely due to a shared epitope region containing a keto sugar component (Sugp) in their repeating units, along with net charge properties similar to serotype 1. These findings revealed novel characteristics of the serotype 38 polysaccharide, including its amino acid composition and net charge, which may contribute to the development of new therapeutics and effective vaccines.