A narrative review of genomic characteristics, serotype, immunogenicity, and vaccine development of Streptococcus pneumoniae capsular polysaccharide

Abstract

This narrative review describes genomic characteristic, serotyping, immunogenicity, and vaccine development of Streptococcus pneumoniae capsular polysaccharide (CPS). CPS is a primary virulence factor of S. pneumoniae. The genomic characteristics of S. pneumoniae CPS, including the role of biosynthetic gene and genetic variation within cps (capsule polysaccharide) locus which may lead to serotype replacement are still being investigated. One hundred unique serotypes of S. pneumoniae have been identified through various methods of serotyping using phenotypic and genotypic approach. The advantages and limitations of each method are various, emphasizing the need for accurate and comprehensive serotyping for effective disease surveillance and vaccine targeting. In addition, we elaborate the critical role of CPS in vaccine development by providing an overview of immunogenicity, ongoing research of pneumococcal vaccines, and the impact on disease burden.

Keywords: Capsular polysaccharide; Immunogenicity; Serotyping; Streptococcus pneumoniae; Vaccine development.

Fig. 1. The Wzx/Wzy-dependent pathway of capsular polysaccharide biosynthesis [45]. Biosynthesis begins with the synthesis of the O-antigen repeat unit in the cytoplasm. The repeat unit is then transferred to a lipid carrier undecaprenyl phosphate (UndP) (A). Glycosyl-transferase will be assembling the repeat unit of monosaccharide (B) before the UndP flipped across the inner membrane to the periplasmic side by Wzx/flippase (C). Wzy polymerase catalyzes the polymerization of the repeat units to form the polysaccharide chain (D), Wzy polymerase adds repeat units one by one to the growing chain and acetyl-coA will be added (E). UDP, uridine diphosphate; dTDP, deoxythymidine diphosphate.

Fig. 2. Synthase-dependent biosynthesis pathway [45]. Serotype 3 PS is created by the Cps3S synthase (structure indicated in the inset). The synthesis is started by Cps3S that transferring glucose (Glc) from uridine diphosphate (UDP)-glucose to a phosphatidyl glycerol (PG) acceptor (A), glucuronic acid (GlcUA) from UDP-GlcUA to the PG-linked Glc (B), Cps3S transport the polysaccharide chain to the outer membrane (C) and added chain length through polymerization (D). UndP, undecaprenyl phosphate; dTDP, deoxythymidine diphosphate.

Fig. 3. Represent genetic differences of vaccine-type cps (capsule polysaccharide) locus among serotypes that found high in prevalence after introduction of pneumococcal conjugate vaccine (PCV)13, leading to development of new PCV [11]. dTDP, deoxythymidine diphosphate; CDP, cytidine diphosphate; UDP, uridine diphosphate.