Protection induced by Streptococcus pneumoniae extracellular vesicles against nasal colonization and invasive infection in mice and the role of PspA

Diseases caused by Streptococcus pneumoniae (pneumococcus) produce a great impact on public health, killing about one million people annually despite available vaccines. Recent research has revealed that the pneumococcus produces extracellular vesicles (pEVs), which display selective cargo and hold potential for vaccine development. Here, we evaluated the immunogenicity and protective potential of pEVs derived from a non-encapsulated pneumococcal strain (R6) using murine models of pneumococcal colonization and invasive pneumonia. Characterization of the immune response revealed that while pEVs contain multiple virulence determinants, immunization with these nanoparticles only induces antibodies against a subset of them. Specifically, subcutaneous immunization elicits a high antibody response against PspA, a modest response against PrsA, and limited response against Ply, MalX and PsaA. The antibody response was further supported by agglutination studies, showing that sera from pEV immunized mice agglutinate pneumococci and that PspA contributes to this response in a strain-dependent manner. Subcutaneous immunization with pEVs provides protection in the invasive pneumonia model whereas nasal immunization results in one log reduction in pneumococcal colonization of the upper respiratory tract. Finally, PspA is a strong contributor to protection in the invasive model and provides a degree of protection even across heterologous families of PspA. We conclude that pEVs demonstrate potential for vaccine development, protecting across capsular types and providing some degree of protection across heterologous PspA variants.