Another plasmid pYA3802 with bla SS-PspA-CT (PspA aa 3–285) was used to probe the protective immune mechanisms of RASVs via the oral route. Park et al. proved that the sIgA is important to RASV-PspA-induced protection against intratracheal (i.t.) challenge using pIgR−/− mice which lack the IgA secretion pathway . Peyer’s patch plays an indispensable role for induction of PspA-specific IgA in both systemic and mucosal compartments. MyD88-mediated innate immunity is not essential for induction of Ag-specific B-cell responses induced by RASV synthesizing T-cell-dependent exogenous Ag, but it is critical for the protection against virulent S. pneumoniae challenge. Influenza infection followed by pneumococcal infection can cause severe pneumonia and this secondary pneumococcal pneumonia is the most common cause of influenza-associated death. Seo et al. tested whether the vaccine against S. pneumoniae could reduce the disease burden caused by seasonal epidemic and pandemic influenza . Mice vaccinated orally with a RASV strain carrying plasmid pYA3802 resulted in attenuated pulmonary inflammation and effective long-term protection against secondary pneumococcal pneumonia after influenza infection . Thus, oral RASV-PspA immunization is not only an efficacious way to protect against respiratory bacterial pathogens, but is also a promising approach against the impact of annual epidemic and pandemic influenza outbreaks. These results highlight the importance of immunizing both the young and elderly populations, which are more susceptible to infection by both S. pneumoniae and influenza, with a RASV against S. pneumoniae.