Enhanced protective responses to a serotype-independent pneumococcal vaccine when combined with an inactivated influenza vaccine

Streptococcus pneumoniae and influenza are the world's foremost bacterial and viral respiratory pathogens. We have previously described a gamma-irradiated influenza A virus (gamma-FLU) vaccine that provides cross-protective immunity against heterosubtypic infections. More recently, we reported a novel non-adjuvanted gamma-irradiated S. pneumoniae (gamma-PN) vaccine that elicits serotype-independent protection. Considering the clinical synergism of both pathogens, combination of a serotype-independent pneumococcal vaccine with a broad-spectrum influenza vaccine to protect against both infections would have a considerable clinical impact. In the present study, we co-immunized C57BL/6 mice intranasally (IN) with a mixture of gamma-PN (whole inactivated cells) and gamma-FLU (whole inactivated virions) and examined protective efficacy. Co-immunization enhanced gamma-PN vaccine efficacy against virulent pneumococcal challenge, which was dependent on CD4(+) T-cell responses. In contrast, vaccination with gamma-PN alone, co-immunization enhanced pneumococcal-specific effector T-helper 17 cell (Th17) and Th1 memory cell, promoted development of CD4(+) tissue-resident memory (TRM) cells and enhanced Pneumococcus-specific antibody responses. Furthermore, co-immunization elicited significant protection against lethal influenza challenge, as well as against co-infection with both influenza and S. pneumoniae. This is the first report showing the synergistic effect of combining whole cell and whole virion vaccines to both S. pneumoniae and influenza as a single vaccine to protect against individual and co-infection, without compromising pathogen-specific immunity.