title: Immune Responses in Acute and Convalescent Patients with Mild, Moderate and Severe Disease during the 2009 Influenza Pandemic in Norway.
abstract: Increased understanding of immune responses influencing clinical severity during pandemic influenza infection is important for improved treatment and vaccine development. In this study we recruited 46 adult patients during the 2009 influenza pandemic and characterized humoral and cellular immune responses. Those included were either acute hospitalized or convalescent patients with different disease severities (mild, moderate or severe). In general, protective antibody responses increased with enhanced disease severity. In the acute patients, we found higher levels of TNF-α single-producing CD4+T-cells in the severely ill as compared to patients with moderate disease. Stimulation of peripheral blood mononuclear cells (PBMC) from a subset of acute patients with peptide T-cell epitopes showed significantly lower frequencies of influenza specific CD8+ compared with CD4+ IFN-γ T-cells in acute patients. Both T-cell subsets were predominantly directed against the envelope antigens (HA and NA). However, in the convalescent patients we found high levels of both CD4+ and CD8+ T-cells directed against conserved core antigens (NP, PA, PB, and M). The results indicate that the antigen targets recognized by the T-cell subsets may vary according to the phase of infection. The apparent low levels of cross-reactive CD8+ T-cells recognizing internal antigens in acute hospitalized patients suggest an important role for this T-cell subset in protective immunity against influenza.
authors.affiliation: The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.|Infectious Diseases Unit, Department of Internal Medicine, Haukeland University Hospital, Bergen, Norway.|K.G. Jebsen Centre for Influenza Vaccine Research, Department of Clinical Science, University of Bergen, Bergen, and The Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Kristin G-I
authors.initials: KG
authors.lastname: Mohn
authors.affiliation: The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Research & Development, Haukeland University Hospital, Bergen, Norway.|K.G. Jebsen Centre for Influenza Vaccine Research, Department of Clinical Science, University of Bergen, Bergen, and The Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Rebecca Jane
authors.initials: RJ
authors.lastname: Cox
authors.affiliation: Division of Infectious Disease Control, Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Oslo, Norway.|K.G. Jebsen Centre for Influenza Vaccine Research, Department of Clinical Science, University of Bergen, Bergen, and The Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Gro
authors.initials: G
authors.lastname: Tunheim
authors.affiliation: Department of Infectious Diseases, Akershus University Hospital, Nordbyhagen, Norway.
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Berdal
authors.affiliation: Section for Virology, Department of Laboratory Services, Norwegian Veterinary Institute, Oslo, Norway.|Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Anna Germundsson
authors.initials: AG
authors.lastname: Hauge
authors.affiliation: The Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Åsne
authors.initials: Å
authors.lastname: Jul-Larsen
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.affiliation: Division of Infectious Disease Control, Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Oslo, Norway.|K.G. Jebsen Centre for Influenza Vaccine Research, Department of Clinical Science, University of Bergen, Bergen, and The Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Oftung
authors.affiliation: Genetic Unit, Department of Multidisciplinary Laboratory Medicine and Medical Biochemistry, Akershus University Hospital, Nordbyhagen, Norway.|Genetic Unit, Centre for Laboratory Medicine, Østfold Hospital Trust, Fredrikstad, Norway.|Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
authors.forename: Christine Monceyron
authors.initials: CM
authors.lastname: Jonassen
authors.affiliation: Division of Infectious Disease Control, Department of Bacteriology and Immunology, Norwegian Institute of Public Health, Oslo, Norway.|K.G. Jebsen Centre for Influenza Vaccine Research, Department of Clinical Science, University of Bergen, Bergen, and The Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Siri
authors.initials: S
authors.lastname: Mjaaland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007109:Immunity; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000175:diagnosis / Q000453:epidemiology* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D009664:Norway / Q000453:epidemiology; D058873:Pandemics; D011446:Prospective Studies; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G