Enhanced protection against nasopharyngeal carriage of Streptococcus pneumoniae elicited by oral multiantigen DNA vaccines delivered in attenuated Salmonella typhimurium.

Developing carrier systems and choosing appropriate antigens are essential steps in improving the safety and efficacy of Streptococcus pneumoniae DNA vaccines, which have enhanced the mucosal protection against nasopharyngeal colonization. In this study, we reconstructed a Salmonella-based balanced-lethal host-eukaryotic vector system, which was used as carrier to orally deliver the Streptococcus pneumoniae multiantigen DNA vaccines encoding psaA (pneumococcal surface adhesion A) and pspA' (N-terminal of pneumococcal surface protein A) genes. The results showed that the multiantigen DNA vaccines using the new vector system as carrier afforded better protection than the vaccination with injected intramuscularly (i.m.) against Streptococcus pneumoniae D39 colonization infection in BALB/c mice models. This finding has associated with a high level of sIgA in the nasal mucosa as well as systemic IgG antibodies and a shift toward a Th1-mediated immune response. These studies have demonstrated the feasibility and advantage of using the new Salmonella-based balanced-lethal host-eukaryotic vector system as carrier to deliver S. pneumoniae DNA vaccines.