title: Genome-Wide Analysis of Evolutionary Markers of Human Influenza A(H1N1)pdm09 and A(H3N2) Viruses May Guide Selection of Vaccine Strain Candidates.
abstract: Here we analyzed whole-genome sequences of 3,969 influenza A(H1N1)pdm09 and 4,774 A(H3N2) strains that circulated during 2009-2015 in the world. The analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza A(H1N1)pdm09 and A(H3N2) strains, respectively. Many of these changes were introduced as a result of random drift. However, there were 61 and 68 changes that were present in relatively large number of A(H1N1)pdm09 and A(H3N2) strains, respectively, that circulated during relatively long time. We named these amino acid substitutions evolutionary markers, as they seemed to contain valuable information regarding the viral evolution. Interestingly, influenza A(H1N1)pdm09 and A(H3N2) viruses acquired non-overlapping sets of evolutionary markers. We next analyzed these characteristic markers in vaccine strains recommended by the World Health Organization for the past five years. Our analysis revealed that vaccine strains carried only few evolutionary markers at antigenic sites of viral hemagglutinin (HA) and neuraminidase (NA). The absence of these markers at antigenic sites could affect the recognition of HA and NA by human antibodies generated in response to vaccinations. This could, in part, explain moderate efficacy of influenza vaccines during 2009-2014. Finally, we identified influenza A(H1N1)pdm09 and A(H3N2) strains, which contain all the evolutionary markers of influenza A strains circulated in 2015, and which could be used as vaccine candidates for the 2015/2016 season. Thus, genome-wide analysis of evolutionary markers of influenza A(H1N1)pdm09 and A(H3N2) viruses may guide selection of vaccine strain candidates.
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Sergei S
authors.initials: SS
authors.lastname: Belanov
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Dmitrii
authors.initials: D
authors.lastname: Bychkov
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Christian
authors.initials: C
authors.lastname: Benner
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland Welcome Trust Sanger Institute, Cambridgeshire, United Kingdom.
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.
authors.forename: Teija
authors.initials: T
authors.lastname: Ojala
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Kankainen
authors.affiliation: Department of Laboratory Medicine, National University Hospital, National University Health System, Singapore.
authors.forename: Hong
authors.initials: H
authors.lastname: Kai Lee
authors.affiliation: Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
authors.forename: Julian
authors.initials: J
authors.lastname: Wei-Tze Tang
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland denis.kainov@helsinki.fi.
authors.forename: Denis E
authors.initials: DE
authors.lastname: Kainov
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D019143:Evolution, Molecular; D005819:Genetic Markers; D016679:Genome, Viral; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000235:genetics*; D008969:Molecular Sequence Data
chemical_list: D005819:Genetic Markers; D007252:Influenza Vaccines
keywords: evolutionary markers; influenza vaccine; influenza virus; virus evolution