title: Vaccination against the M protein of Streptococcus pyogenes prevents death after influenza virus: S. pyogenes super-infection.
abstract: Influenza virus infections are associated with a significant number of illnesses and deaths on an annual basis. Many of the deaths are due to complications from secondary bacterial invaders, including Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes. The β-hemolytic bacteria S. pyogenes colonizes both skin and respiratory surfaces, and frequently presents clinically as strep throat or impetigo. However, when these bacteria gain access to normally sterile sites, they can cause deadly diseases including sepsis, necrotizing fasciitis, and pneumonia. We previously developed a model of influenza virus:S. pyogenes super-infection, which we used to demonstrate that vaccination against influenza virus can limit deaths associated with a secondary bacterial infection, but this protection was not complete. In the current study, we evaluated the efficacy of a vaccine that targets the M protein of S. pyogenes to determine whether immunity toward the bacteria alone would allow the host to survive an influenza virus:S. pyogenes super-infection. Our data demonstrate that vaccination against the M protein induces IgG antibodies, in particular those of the IgG1 and IgG2a isotypes, and that these antibodies can interact with macrophages. Ultimately, this vaccine-induced immunity eliminated death within our influenza virus:S. pyogenes super-infection model, despite the fact that all M protein-vaccinated mice showed signs of illness following influenza virus inoculation. These findings identify immunity against bacteria as an important component of protection against influenza virus:bacteria super-infection.
authors: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.
authors: Joshua M
authors: JM
authors: Klonoski
authors: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.
authors: Heather R
authors: HR
authors: Hurtig
authors: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.
authors: Brian A
authors: BA
authors: Juber
authors: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.
authors: Margaret J
authors: MJ
authors: Schuneman
authors: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.
authors: Thomas E
authors: TE
authors: Bickett
authors: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.
authors: Joshua M
authors: JM
authors: Svendsen
authors: Department of Chemistry, University of South Dakota, Vermillion, SD, United States.
authors: Brandon
authors: B
authors: Burum
authors: University of Tennessee Health Science Center and the Veterans Affairs Medical Center Research Service, Memphis, TN, United States.
authors: Thomas A
authors: TA
authors: Penfound
authors: Department of Chemistry, University of South Dakota, Vermillion, SD, United States.
authors: Grigoriy
authors: G
authors: Sereda
authors: University of Tennessee Health Science Center and the Veterans Affairs Medical Center Research Service, Memphis, TN, United States.
authors: James B
authors: JB
authors: Dale
authors: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.
authors: Michael S
authors: MS
authors: Chaussee
authors: Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States. Electronic address: victor.huber@usd.edu.
authors: Victor C
authors: VC
authors: Huber
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002460:Cell Line; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009975:Orthomyxoviridae; D009976:Orthomyxoviridae Infections / Q000150:complications*; D013290:Streptococcal Infections / Q000150:complications / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes; D015163:Superinfection
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D007074:Immunoglobulin G; D022541:Streptococcal Vaccines; C014689:streptococcal M protein
keywords: Bacteria; Influenza; Super-infection