Disease modulation by TIV vaccination during secondary pneumococcal infections in influenza-infected mice

ABSTRACT Secondary bacterial infections can significantly worsen the clinical course of influenza virus infections and are a leading cause of morbidity and mortality during seasonal influenza epidemics. Despite being a vaccine-preventable disease, influenza-related complications from secondary bacterial infections are an important cause of death, particularly among the elderly population. Streptococcus pneumoniae (Spn) is the most common agent responsible for influenza-related secondary bacterial infections. Influenza virus vaccination serves as an effective prophylactic strategy for preventing influenza and reducing the burden of influenza-associated pathology, including secondary bacterial infection. However, whether the protective effects of influenza virus vaccination differ in the context of a secondary Spn infection at the level of the host response remains poorly characterized. Here, we present a preclinical mouse model to examine the impact of influenza vaccination in scenarios involving single infections with influenza A virus H1N1 (NC99) or Spn serotype 1; simultaneous infection with both NC99 and Spn (coinfection), or NC99 infection followed by Spn infection seven days later (superinfection). A single dose of trivalent inactivated Influenza vaccine (TIV) is able to decrease infection lethality in both secondary bacterial infection scenarios. Protection is associated with reduction in both viral and bacterial titers, decreased production of pro-inflammatory cytokines, protection of alveolar macrophages, prevention of exacerbated lung neutrophil recruitment, modulation of neutrophil activation status, and induction of lung eosinophil recruitment and activation. These findings underscore the importance of influenza vaccination in modulating disease progression and preventing morbidity and mortality associated with secondary bacterial infections. IMPORTANCE In this study, we show that a licensed influenza vaccine not only prevents severe disease upon influenza virus infection but also helps protect against enhanced morbidity due to co- or superinfection with S treptococcus pneumoniae in a mouse model. This protection correlates with better control of viral and bacterial titers, as well as with altered host immune responses during bacterial co- and superinfection, characterized by the recruitment of activated granulocytes.