Synthesis and delivery of <i>Streptococcus pneumoniae</i> capsular polysaccharides by recombinant attenuated <i>Salmonella</i> vaccines.

Abstract

<i>Streptococcus pneumoniae</i> capsular polysaccharides (CPSs) are major determinants of bacterial pathogenicity. CPSs of different serotypes form the main components of the pneumococcal vaccines Pneumovax, Prevnar7, and Prevnar13, which substantially reduced the <i>S. pneumoniae</i> disease burden in developed countries. However, the laborious production processes of traditional polysaccharide-based vaccines have raised the cost of the vaccines and limited their impact in developing countries. The aim of this study is to develop a kind of low-cost live vaccine based on using the recombinant attenuated <i>Salmonella</i> vaccine (RASV) system to protect against pneumococcal infections. We cloned genes for seven different serotypes of CPSs to be expressed by the RASV strain. Oral immunization of mice with the RASV-CPS strains elicited robust Th1 biased adaptive immune responses. All the CPS-specific antisera mediated opsonophagocytic killing of the corresponding serotype of <i>S. pneumoniae</i> in vitro. The RASV-CPS2 and RASV-CPS3 strains provided efficient protection of mice against challenge infections with either <i>S. pneumoniae</i> strain D39 or WU2. Synthesis and delivery of <i>S. pneumoniae</i> CPSs using the RASV strains provide an innovative strategy for low-cost pneumococcal vaccine development, production, and use.