Streptococcus pneumoniae Attenuated Strain SPY1 with an Artificial Mineral Shell Induces Humoral and Th17 Cellular Immunity and Protects Mice against Pneumococcal Infection

摘要

Streptococcus pneumoniae is a major pathogen leading to substantial morbidity and mortality in children under 5?years of age. Vaccination is an effective strategy to prevent S. pneumoniae infection. SPY1 is a pneumococcal vaccine candidate strain obtained in our previous study. To improve its stability and immunogencity, in this study, we constructed the SPY1Δ lytA strain that lacks autolysin activity and was coated with an artificial exterior surface calcium phosphate shell by in situ mineralization. The resulting strain SPY1Δ lytA CaPi displayed enhanced thermal stability enabling storage at 37°C for 1?week. Furthermore, mucosal and subcutaneous immunization with the SPY1Δ lytA CaPi strain induced better protective effects than SPY1Δ lytA in anti-colonization after challenging with 19F and anti-invasion by D39 in mice. Subcutaneous immunization with SPY1Δ lytA CaPi elicited higher IgG level while mucosal immunization primarily elicited an immune response which is supposed to be related to Th17?cells. Taken together, the mineralized strain may be a promising candidate for an attenuated S. pneumoniae vaccine.