Human infection with influenza poses a significant annual global health threat, especially when complicated by secondary bacterial infections. During the recent H1N1 pandemic, Streptococcus pyogenes (GAS) caused about 1/3 of the deaths associated with bacterial secondary infections. Viral infections of the upper respiratory tract, particularly influenza, are also linked to the development of invasive GAS infections other than pneumonia, including bacteremia, toxic shock syndrome, and necrotizing fasciitis. The mortality rates of these infections are high, despite the use of influenza vaccines, antivirals, an antibiotics. A better understanding of the coinfection process and additional treatment options are needed to effectively control influenza-associated mortality. We hypothesize that treating coinfections with antibodies targeting bacterial proteins important to establishing the coinfection will mitigate morbidity and mortality. To test this hypothesis, we propose two aims that utilize ou established influenza A virus (IAV)-GAS mouse model of coinfection. In the first, we will determine if the loss of specific GAS pathogenesis factors alters the ability of the bacteria to establish and maintain a coinfection with IAV. In the second, we will determine if passive administration of antibodies against these factors can alter the morbidity and mortality associated with coinfection. If successful, the results could be leveraged to eventually create a multivalent passive vaccination immunotherapy designed to prevent, or treat, IAV coinfections caused by S. pneumoniae, S. aureus, H. influenzae, and GAS, which could save lives during influenza epidemics and pandemics.
Influenza causes an average of 36,000 deaths on an annual basis in the U.S., often as the result of secondary bacterial infections or coinfections. During th recent influenza pandemic, Streptococcus pyogenes caused about a third of these deaths. Despite the use of influenza vaccines, antivirals, and antibiotics, the mortality of coinfection is remarkably high and additional therapeutic options are needed. The project will test the efficacy of using passively administered antibodies to bacterial targets critical to the establishment of a coinfection as a means of preventing and/or treating influenza coinfections. Such intervention could save lives during influenza epidemics and pandemics.
