Vaccination with formalin-inactivated influenza vaccine protects mice against lethal influenza Streptococcus pyogenes superinfection.

Intranasal infection with non-lethal influenza A virus (IAV) followed by infection with group A streptococci (GAS) induces invasive, lethal GAS infections, including necrotizing fasciitis, in mice. We demonstrate that subcutaneous immunization of formalin-inactivated IAV vaccine or intranasal immunization of IAV vaccine and cholera toxin protected more than 75% of mice from death by lethal IAV-GAS superinfection. The increased survival rate correlates with increase in IAV neutralizing activity and the levels of serum anti-IAV IgG. Moreover, elimination of IAV from the lungs of vaccinated mice led to depletion of GAS associated with alveolar epithelial cells. These findings suggest that formalin-inactivated IAV vaccine may be useful for prevention of secondary bacterial infections following prior IAV exposure.