title: Inactivated and live, attenuated influenza vaccines protect mice against influenza: Streptococcus pyogenes super-infections.
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.
authors: Division of Basic Biomedical Sciences, University of South Dakota, Vermillion, SD, United States.
authors: Michael S
authors: MS
authors: Chaussee
authors: Heather R
authors: HR
authors: Sandbulte
authors: Margaret J
authors: MJ
authors: Schuneman
authors: Frank P
authors: FP
authors: Depaula
authors: Leslie A
authors: LA
authors: Addengast
authors: Evelyn H
authors: EH
authors: Schlenker
authors: Victor C
authors: VC
authors: Huber
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000032:analysis* / Q000097:blood; D000914:Antibodies, Viral / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology / Q000821:virology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D018928:Immunity, Mucosal / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D013290:Streptococcal Infections / Q000517:prevention & control*; D013297:Streptococcus pyogenes / Q000276:immunology; D015163:Superinfection / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated