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Updated: Jun 3, 2026
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Inactivated and live, attenuated influenza vaccines protect mice against influenza: Streptococcus pyogenes
Michael S Chaussee1, Heather R Sandbulte, Margaret J Schuneman
1Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, SD, United States.
Abstract:
Mortality associated with influenza virus super-infections is frequently due to secondary bacterial complications. To date, super-infections with Streptococcus pyogenes have been studied less extensively than those associated with Streptococcus pneumoniae. This is significant because a vaccine for S. pyogenes is not clinically available, leaving vaccination against influenza virus as our only means for preventing these super-infections. In this study, we directly compared immunity induced by two types of influenza vaccine, either inactivated influenza virus (IIV) or live, attenuated influenza virus (LAIV), for the ability to prevent super-infections. Our data demonstrate that both IIV and LAIV vaccines induce similar levels of serum antibodies, and that LAIV alone induces IgA expression at mucosal surfaces. Upon super-infection, both vaccines have the ability to limit the induction of pro-inflammatory cytokines within the lung, including IFN-γ which has been shown to contribute to mortality in previous models of super-infection. Limiting expression of these pro-inflammatory cytokines within the lungs subsequently limits recruitment of macrophages and neutrophils to pulmonary surfaces, and ultimately protects both IIV- and LAIV-vaccinated mice from mortality. Despite their overall survival, both IIV- and LAIV-vaccinated mice demonstrated levels of bacteria within the lung tissue that are similar to those seen in unvaccinated mice. Thus, influenza virus:bacteria super-infections can be limited by vaccine-induced immunity against influenza virus, but the ability to prevent morbidity is not complete.
Insights
Influenza virus vaccination, using inactivated (IIV) or live attenuated (LAIV) vaccines, protects mice from death due to secondary bacterial superinfections. However, it does not fully prevent bacterial growth in the lungs.
Area of Science:
- Immunology
- Virology
- Microbiology
Background:
- Influenza virus superinfections with bacteria, particularly Streptococcus pyogenes, cause significant mortality.
- Vaccines against S. pyogenes are unavailable, making influenza virus vaccination crucial for prevention.
- Previous studies highlight the role of pro-inflammatory cytokines like IFN-γ in superinfection-associated mortality.
Purpose of the Study:
- To compare the efficacy of inactivated influenza virus (IIV) and live, attenuated influenza virus (LAIV) vaccines in preventing influenza virus-bacteria superinfections.
- To investigate the immune responses induced by IIV and LAIV against secondary bacterial complications.
Main Methods:
- Mice were vaccinated with either IIV or LAIV.
- Vaccinated and unvaccinated mice were subsequently infected with influenza virus and then challenged with Streptococcus pyogenes.
- Immune responses, including antibody levels, cytokine expression (IFN-γ), and immune cell recruitment (macrophages, neutrophils), were analyzed.
- Bacterial load in lung tissue was quantified.
Main Results:
- Both IIV and LAIV induced comparable levels of serum antibodies against influenza virus.
- LAIV uniquely induced IgA expression at mucosal surfaces.
- Both vaccines limited the induction of pro-inflammatory cytokines (e.g., IFN-γ) in the lungs upon superinfection.
- Vaccination protected mice from mortality by reducing pro-inflammatory responses and immune cell infiltration.
- Despite survival, bacterial loads in the lungs of vaccinated mice were similar to unvaccinated controls.
Conclusions:
- Influenza virus vaccination (IIV and LAIV) effectively reduces mortality associated with bacterial superinfections.
- Vaccine-induced immunity mitigates the detrimental pro-inflammatory response in the lungs.
- While survival is improved, influenza vaccination does not completely clear bacterial superinfections, indicating incomplete protection against morbidity.
