title: Selection of antigenically advanced variants of seasonal influenza viruses.
abstract: Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014-2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Chengjun
authors: C
authors: Li
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Masato
authors: M
authors: Hatta
authors: Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.|World Health Organization Collaborating Centre for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK.
authors: David F
authors: DF
authors: Burke
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Jihui
authors: J
authors: Ping
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Ying
authors: Y
authors: Zhang
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.|Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors: Makoto
authors: M
authors: Ozawa
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Andrew S
authors: AS
authors: Taft
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Subash C
authors: SC
authors: Das
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Anthony P
authors: AP
authors: Hanson
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Jiasheng
authors: J
authors: Song
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.|Department of Veterinary Medicine, Faculty of Agriculture, Iwate University, Iwate 020-8550, Japan.
authors: Masaki
authors: M
authors: Imai
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Peter R
authors: PR
authors: Wilker
authors: ERATO Infection-Induced Host Responses Project, Saitama 332-0012, Japan.
authors: Tokiko
authors: T
authors: Watanabe
authors: ERATO Infection-Induced Host Responses Project, Saitama 332-0012, Japan.
authors: Shinji
authors: S
authors: Watanabe
authors: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors: Mutsumi
authors: M
authors: Ito
authors: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors: Kiyoko
authors: K
authors: Iwatsuki-Horimoto
authors: World Health Organization Collaborating Centre for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK.|Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.|Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
authors: Colin A
authors: CA
authors: Russell
authors: Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.|World Health Organization Collaborating Centre for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK.
authors: Sarah L
authors: SL
authors: James
authors: Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.|World Health Organization Collaborating Centre for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK.
authors: Eugene
authors: E
authors: Skepner
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Eileen A
authors: EA
authors: Maher
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors: Gabriele
authors: G
authors: Neumann
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30033, USA.
authors: Alexander I
authors: AI
authors: Klimov
authors: WHO Collaborating Centre for Reference and Research on Influenza (VIDRL) at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors: Anne
authors: A
authors: Kelso
authors: Division of Virology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
authors: John
authors: J
authors: McCauley
authors: Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors: Dayan
authors: D
authors: Wang
authors: Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors: Yuelong
authors: Y
authors: Shu
authors: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashi-Murayama, Tokyo 208-0011, Japan.
authors: Takato
authors: T
authors: Odagiri
authors: Influenza Virus Research Center, National Institute of Infectious Diseases, Musashi-Murayama, Tokyo 208-0011, Japan.
authors: Masato
authors: M
authors: Tashiro
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30033, USA.
authors: Xiyan
authors: X
authors: Xu
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30033, USA.
authors: David E
authors: DE
authors: Wentworth
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30033, USA.
authors: Jacqueline M
authors: JM
authors: Katz
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30033, USA.
authors: Nancy J
authors: NJ
authors: Cox
authors: Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.|World Health Organization Collaborating Centre for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK.|Department of Virology, Erasmus Medical Center, 3000 CA Rotterdam, Netherlands.
authors: Derek J
authors: DJ
authors: Smith
authors: Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.|Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.|ERATO Infection-Induced Host Responses Project, Saitama 332-0012, Japan.|Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors: Yoshihiro
authors: Y
authors: Kawaoka
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D019143:Evolution, Molecular; D005289:Ferrets / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000453:epidemiology / Q000517:prevention & control*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D012621:Seasons
chemical_list: D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines