Effective protection against secondary pneumococcal pneumonia by oral vaccination with attenuated Salmonella delivering PspA antigen in mice

Influenza infection followed by pneumococcal infection can cause severe pneumonia and this secondary pneumococcal pneumonia is the most common cause of influenza-associated death. Therefore, vaccination against Streptococcus pneumoniae is highly desirable for reducing the disease burden caused by seasonal epidemic and pandemic influenza. In this study, mice were vaccinated orally with a recombinant attenuated Salmonella vaccine (RASV) strain that delivers pneumococcal surface protein A (PspA) in order to examine protective efficacy against secondary pneumococcal pneumonia. A single dose of oral RASV resulted in attenuated pulmonary inflammation and effective protection against secondary pneumococcal pneumonia. Additionally, oral RASV induced long-term protection against secondary pneumococcal pneumonia. Treatment with an antiviral drug (i.e., oseltamivir) after treatment with RASV further prevented pulmonary inflammation after secondary pneumococcal infection. These results imply that oral RASV can protect mice from secondary pneumococcal infection after influenza infection and that vaccination against respiratory bacterial pathogens is a promising approach for dampening the impact of annual epidemic and pandemic influenza outbreaks.