title: High conservation level of CD8(+) T cell immunogenic regions within an unusual H1N2 human influenza variant.
abstract: Current seasonal influenza vaccines require regular updates due to antigenic drift causing loss of effectiveness and therefore providing little or no protection against novel influenza A subtypes. Next generation vaccines capable of eliciting CD8(+) T cell (CTL) mediated cross-protective immunity may offer a long-term alternative strategy. However, measuring pre- and existing levels of CTL cross-protection in humans is confounded by differences in infection histories across individuals. During 2000-2003, H1N2 viruses circulated persistently in the human population for the first time and we hypothesized that the viral nucleoprotein (NP) contained novel CTL epitopes that may have contributed to the survival of the viruses. This study describes the immunogenic NP peptides of H1N1, H2N2, and H3N2 influenza viruses isolated from humans over the past century, 1918-2003, by comparing this historical dataset to reference NP peptides from H1N2 that circulated in humans during 2000-2003. Observed peptides sequences ranged from highly conserved (15%) to highly variable (12%), with variation unrelated to reported immunodominance. No unique NP peptides which were exclusive to the H1N2 viruses were noted. However, the virus had inherited the NP from a recently emerged H3N2 variant containing novel peptides, which may have assisted its persistence. Any advantage due to this novelty was subsequently lost with emergence of a newer H3N2 variant in 2003. Our approach has potential to provide insight into the population context in which influenza viruses emerge, and may help to inform immunogenic peptide selection for CTL-inducing influenza vaccines. J. Med. Virol. 88:1725-1732, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia.|Monash University, Melbourne, Victoria, Australia.|The Peter Doherty Institute of Infection and Immunity, Melbourne, Australia.
authors.forename: Naomi
authors.initials: N
authors.lastname: Komadina
authors.affiliation: The Peter Doherty Institute of Infection and Immunity, Melbourne, Australia.|The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Sergio M
authors.initials: SM
authors.lastname: Quiñones-Parra
authors.affiliation: The Peter Doherty Institute of Infection and Immunity, Melbourne, Australia.|The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
authors.affiliation: The University of Melbourne, Melbourne, Victoria, Australia.|Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: James M
authors.initials: JM
authors.lastname: McCaw
authors.affiliation: World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia.|The Peter Doherty Institute of Infection and Immunity, Melbourne, Australia.|The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Kelso
authors.affiliation: Monash University, Melbourne, Victoria, Australia.|Victorian Infectious Diseases Services, Melbourne, Victoria, Australia.
authors.forename: Karin
authors.initials: K
authors.lastname: Leder
authors.affiliation: The University of Melbourne, Melbourne, Victoria, Australia.|Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: Jodie
authors.initials: J
authors.lastname: McVernon
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D056738:Cross Protection; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000276:immunology; D057221:Influenza A Virus, H1N2 Subtype / Q000235:genetics* / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000737:chemistry / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D010455:Peptides / Q000276:immunology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D010455:Peptides; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins
keywords: H1N2; cross-protection; immunogenic; influenza; peptides