title: Influenza gain-of-function experiments: their role in vaccine virus recommendation and pandemic preparedness.
abstract: In recent years, controversy has arisen regarding the risks and benefits of certain types of gain-of-function (GOF) studies involving avian influenza viruses. In this article, we provide specific examples of how different types of data, including information garnered from GOF studies, have helped to shape the influenza vaccine production process-from selection of candidate vaccine viruses (CVVs) to the manufacture and stockpiling of safe, high-yield prepandemic vaccines for the global community. The article is not written to support a specific pro- or anti-GOF stance but rather to inform the scientific community about factors involved in vaccine virus selection and the preparation of prepandemic influenza vaccines and the impact that some GOF information has had on this process.
authors.affiliation: WHO Collaborating Center for Studies on the Ecology of Influenza in Animals, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Stacey.schultz-cherry@stjude.org.
authors.forename: S
authors.initials: S
authors.lastname: Schultz-Cherry
authors.affiliation: WHO Collaborating Center for Studies on the Ecology of Influenza in Animals, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Webby
authors.affiliation: WHO Collaborating Center for Studies on the Ecology of Influenza in Animals, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Webster
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Kelso
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
authors.forename: I G
authors.initials: IG
authors.lastname: Barr
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, Division of Virology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom.
authors.forename: J W
authors.initials: JW
authors.lastname: McCauley
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, Division of Virology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom.
authors.forename: R S
authors.initials: RS
authors.lastname: Daniels
authors.affiliation: WHO Collaborating Center for Reference and Research on Influenza, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention China CDC, Beijing, People's Republic of China.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.affiliation: WHO Collaborating Center for Reference and Research on Influenza, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention China CDC, Beijing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shu
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Laboratory of Influenza Virus Surveillance, Influenza Virus Research Center, Tokyo, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Nobusawa
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Laboratory of Influenza Virus Surveillance, Influenza Virus Research Center, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Itamura
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Laboratory of Influenza Virus Surveillance, Influenza Virus Research Center, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Laboratory of Influenza Virus Surveillance, Influenza Virus Research Center, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Harada
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Laboratory of Influenza Virus Surveillance, Influenza Virus Research Center, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Laboratory of Influenza Virus Surveillance, Influenza Virus Research Center, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Odagiri
authors.affiliation: Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Immunology and Vaccines, Therapeutic Goods Administration Laboratories, Woden, ACT, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Grohmann
authors.affiliation: National Institute for Biological Standards and Control, Medicines and Healthcare Products Regulatory Agency, Potters Bar, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Harvey
authors.affiliation: National Institute for Biological Standards and Control, Medicines and Healthcare Products Regulatory Agency, Potters Bar, United Kingdom.
authors.forename: O
authors.initials: O
authors.lastname: Engelhardt
authors.affiliation: Center for Pathogen Evolution, Department of Zoology, WHO CC for Modeling Evolution and Control of Emerging Infectious Diseases, University of Cambridge, Cambridge, United Kingdom.
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.affiliation: OIE Scientific and Technical Department, OIE, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Hamilton
authors.affiliation: OFFLU/EMPRES Laboratory Unit, Animal Health Service, FAO, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Claes
authors.affiliation: OFFLU/EMPRES Laboratory Unit, Animal Health Service, FAO, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Dauphin
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D007252:Influenza Vaccines / Q000276:immunology / Q000302:isolation & purification*; D005585:Influenza in Birds / Q000635:transmission / Q000821:virology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D058873:Pandemics / Q000517:prevention & control*; D011200:Poultry; D013678:Technology, Pharmaceutical / Q000379:methods; D015047:Zoonoses / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology
chemical_list: D007252:Influenza Vaccines