title: H1N1 viral proteome peptide microarray predicts individuals at risk for H1N1 infection and segregates infection versus Pandemrix(®) vaccination.
abstract: A high content peptide microarray containing the entire influenza A virus [A/California/08/2009(H1N1)] proteome and haemagglutinin proteins from 12 other influenza A subtypes, including the haemagglutinin from the [A/South Carolina/1/1918(H1N1)] strain, was used to gauge serum IgG epitope signatures before and after Pandemrix(®) vaccination or H1N1 infection in a Swedish cohort during the pandemic influenza season 2009. A very narrow pattern of pandemic flu-specific IgG epitope recognition was observed in the serum from individuals who later contracted H1N1 infection. Moreover, the pandemic influenza infection generated IgG reactivity to two adjacent epitopes of the neuraminidase protein. The differential serum IgG recognition was focused on haemagglutinin 1 (H1) and restricted to classical antigenic sites (Cb) in both the vaccinated controls and individuals with flu infections. We further identified a novel epitope VEPGDKITFEATGNL on the Ca antigenic site (251-265) of the pandemic flu haemagglutinin, which was exclusively recognized in serum from individuals with previous vaccinations and never in serum from individuals with H1N1 infection (confirmed by RNA PCR analysis from nasal swabs). This epitope was mapped to the receptor-binding domain of the influenza haemagglutinin and could serve as a correlate of immune protection in the context of pandemic flu. The study shows that unbiased epitope mapping using peptide microarray technology leads to the identification of biologically and clinically relevant target structures. Most significantly an H1N1 infection induced a different footprint of IgG epitope recognition patterns compared with the pandemic H1N1 vaccine.
authors: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors: Aditya
authors: http://orcid.org/0000-0001-8462-3552
authors: A
authors: Ambati
authors: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors: Davide
authors: D
authors: Valentini
authors: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors: Emanuele
authors: E
authors: Montomoli
authors: VisMederi srl, Enterprise in Life Science, Siena, Italy.
authors: Guilia
authors: G
authors: Lapini
authors: VisMederi srl, Enterprise in Life Science, Siena, Italy.
authors: Fabrizio
authors: F
authors: Biuso
authors: JPT Peptide Technologies, Berlin, Germany.
authors: Holger
authors: H
authors: Wenschuh
authors: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors: Isabelle
authors: I
authors: Magalhaes
authors: Therapeutic Immunology Unit, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.|Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
authors: Markus
authors: M
authors: Maeurer
mesh_terms: D000595:Amino Acid Sequence; D015331:Cohort Studies; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D020543:Proteome / Q000276:immunology* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D012307:Risk Factors; D014611:Vaccination / Q000379:methods
chemical_list: D000939:Epitopes; D006389:Hemagglutinins, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D020543:Proteome; C556153:pandemrix; D009439:Neuraminidase
keywords: epitopes; haemagglutinin; immunoglobulin G; influenza; peptide microarray; vaccination
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