Limited Efficacy of Antibacterial Vaccination Against Secondary Serotype 3 Pneumococcal Pneumonia Following Influenza Infection

[[[ Background: ]]] Secondary bacterial infections following influenza represent a major cause of mortality in the human population, which, in turn, has led to a call for stockpiling of bacterial vaccines for pandemic preparedness. [[[ Methods: ]]] To investigate the efficacy of bacterial vaccination for protection against secondary pneumococcal infection, mice were immunized with pneumococcal capsular polysaccharide conjugate vaccine, and then sequentially coinfected 5 weeks later with PR8 influenza virus and A66.1 Streptococcus pneumoniae. [[[ Results: ]]] In the absence of influenza virus exposure, vaccination with polysaccharide conjugate vaccine was highly effective, as indicated by 100% survival from lethal pneumococcal pneumonia and 10 000-fold greater efficiency in clearance of bacteria from the lung compared to unvaccinated mice. Enhanced clearance after vaccination was dependent upon Fc receptor (FcR) expression. However, following influenza, <40% of vaccinated mice survived bacterial coinfection and FcR-dependent clearance of antibody-opsonized bacteria reduced bacterial levels in the lungs only 5-10 fold. No differences in lung myeloid cell numbers or in FcR cell surface expression were observed following influenza. [[[ Conclusions: ]]] The results show that induction of antibacterial humoral immunity is only partially effective in protection against secondary bacterial infections that occur following influenza, and suggest that additional therapeutic strategies to overcome defective antibacterial immunity should be explored.