Intranasal vaccination with pneumococcal surface protein A and interleukin-12 augments antibody-mediated opsonization and protective immunity againstStreptococcus pneumoniae infection

Streptococcus pneumoniae is a major pathogen in humans that enters the host primarily through the respiratory tract. Targeting mucosal surfaces direct ly may therefore be an optimal approach for vaccination to prevent bacteria l colonization and invasive disease. We have previously demonstrated the ef fectiveness of interleukin-12 (IL-12) delivered intransally (i.n.) as an an tiviral respiratory adjuvant. In this study, we examined the effects of i.n . IL-12 treatment on induction of protective Immoral immunity against S. pn eumoniae. Immunization i.n. with pneumococcal surface protein A (PspA) and IL-12 resulted in enhanced lung IL-10 mRNA expression and marked augmentati on of respiratory and systemic immunoglobulin G1 (IgG1), IgG2a, and IgA ant ibody levels compared to those in animals receiving PspA alone. In addition , i.n. vaccination with PspA and IL-12 provided increased protection agains t nasopharyngeal carriage. Flow cytometric analysis revealed a threefold in crease in antibody-mediated, complement-independent opsonic activity in the sera of PspA- and IL-12-treated animals, which was mainly contributed by I gG2a and, to a lesser extent, IgA. Passive transfer of these immune sera co nferred complete protection from death upon systemic pneumococcal challenge . These findings demonstrate the effectiveness of combining PspA and IL-12 at mucosal sites to achieve optimal antibody-mediated opsonization and kill ing of S. pneumoniae.