Influenza gain-of-function experiments: their role in vaccine virus recommendation and pandemic preparedness

doi:10.1128/mBio.02430-14

Editorial

. 2014 Dec 12;5(6):e02430-14.

doi: 10.1128/mBio.02430-14.

Influenza gain-of-function experiments: their role in vaccine virus recommendation and pandemic preparedness

S Schultz-Cherry¹, R J Webby², R G Webster², A Kelso³, I G Barr³, J W McCauley⁴, R S Daniels⁴, D Wang⁵, Y Shu⁵, E Nobusawa⁶, S Itamura⁶, M Tashiro⁶, Y Harada⁶, S Watanabe⁶, T Odagiri⁶, Z Ye⁷, G Grohmann⁸, R Harvey⁹, O Engelhardt⁹, D Smith¹⁰, K Hamilton¹¹, F Claes¹², G Dauphin¹²

Affiliations

¹ 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.
² 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.
³ WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁴ WHO Collaborating Centre for Reference and Research on Influenza, Division of Virology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom.
⁵ 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.
⁶ 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.
⁷ Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA.
⁸ Immunology and Vaccines, Therapeutic Goods Administration Laboratories, Woden, ACT, Australia.
⁹ National Institute for Biological Standards and Control, Medicines and Healthcare Products Regulatory Agency, Potters Bar, United Kingdom.
¹⁰ Center for Pathogen Evolution, Department of Zoology, WHO CC for Modeling Evolution and Control of Emerging Infectious Diseases, University of Cambridge, Cambridge, United Kingdom.
¹¹ OIE Scientific and Technical Department, OIE, Paris, France.
¹² OFFLU/EMPRES Laboratory Unit, Animal Health Service, FAO, Rome, Italy.

PMID: 25505124
PMCID: PMC4278542
DOI: 10.1128/mBio.02430-14

Free PMC article

Editorial

Influenza gain-of-function experiments: their role in vaccine virus recommendation and pandemic preparedness

S Schultz-Cherry et al. mBio. 2014.

Free PMC article

. 2014 Dec 12;5(6):e02430-14.

doi: 10.1128/mBio.02430-14.

Authors

Affiliations

¹ 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.
² 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.
³ WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁴ WHO Collaborating Centre for Reference and Research on Influenza, Division of Virology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom.
⁵ 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.
⁶ 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.
⁷ Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland, USA.
⁸ Immunology and Vaccines, Therapeutic Goods Administration Laboratories, Woden, ACT, Australia.
⁹ National Institute for Biological Standards and Control, Medicines and Healthcare Products Regulatory Agency, Potters Bar, United Kingdom.
¹⁰ Center for Pathogen Evolution, Department of Zoology, WHO CC for Modeling Evolution and Control of Emerging Infectious Diseases, University of Cambridge, Cambridge, United Kingdom.
¹¹ OIE Scientific and Technical Department, OIE, Paris, France.
¹² OFFLU/EMPRES Laboratory Unit, Animal Health Service, FAO, Rome, Italy.

PMID: 25505124
PMCID: PMC4278542
DOI: 10.1128/mBio.02430-14

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.

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Figures

**FIG 1**
Phylogenetic analysis of Cambodian HPAI H5N1 clade 1 viruses. Phylogenetic tree of Cambodian HPAI H5N1 clade 1 HA genes as rooted to the A/Vietnam/1203/2004 CVV.

**FIG 2**
Generation of recombinant vaccines for influenza by reverse genetics. From the National Institute of Allergy and Infectious Diseases.

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References

1. World Health Organization 2008, posting date Influenza. World Health Organization, Geneva, Switzerland. http://www.who.int/immunization/topics/influenza/en/.
1. Freidl GS, Meijer A, de Bruin E, de Nardi M, Munoz O, Capua I, Breed AC, Harris K, Hill A, Kosmider R, Banks J, von Dobschuetz S, Stark K, Wieland B, Stevens K, van der Werf S, Enouf V, van der Meulen K, Van Reeth K, Dauphin G, Koopmans M, FLURISK Consortium 2014. Influenza at the animal-human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1). Euro Surveill. 19:pii=20793 http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20793. - PubMed
1. World Health Organization 2014, posting date Avian influenza in humans. WHO, Geneva, Switzerland.
1. Zhu Y, Qi X, Cui L, Zhou M, Wang H. 2013. Human co-infection with novel avian influenza A H7N9 and influenza A H3N2 viruses in Jiangsu province, China. Lancet 381:2134. 10.1016/S0140-6736(13)61135-6. - DOI - PubMed
1. Li J, Kou Y, Yu X, Sun Y, Zhou Y, Pu X, Jin T, Pan J, Gao GF. 2014. Human co-infection with avian and seasonal influenza viruses, china. Emerg. Infect. Dis. 20:1953–1955. 10.3201/eid2011.140897. - DOI - PMC - PubMed

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[1] World Health Organization 2008, posting date Influenza. World Health Organization, Geneva, Switzerland. http://www.who.int/immunization/topics/influenza/en/.

[2] World Health Organization 2008, posting date Influenza. World Health Organization, Geneva, Switzerland. http://www.who.int/immunization/topics/influenza/en/.

[3] Freidl GS, Meijer A, de Bruin E, de Nardi M, Munoz O, Capua I, Breed AC, Harris K, Hill A, Kosmider R, Banks J, von Dobschuetz S, Stark K, Wieland B, Stevens K, van der Werf S, Enouf V, van der Meulen K, Van Reeth K, Dauphin G, Koopmans M, FLURISK Consortium 2014. Influenza at the animal-human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1). Euro Surveill. 19:pii=20793 http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20793. - PubMed

[4] Freidl GS, Meijer A, de Bruin E, de Nardi M, Munoz O, Capua I, Breed AC, Harris K, Hill A, Kosmider R, Banks J, von Dobschuetz S, Stark K, Wieland B, Stevens K, van der Werf S, Enouf V, van der Meulen K, Van Reeth K, Dauphin G, Koopmans M, FLURISK Consortium 2014. Influenza at the animal-human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1). Euro Surveill. 19:pii=20793 http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20793. - PubMed

[5] World Health Organization 2014, posting date Avian influenza in humans. WHO, Geneva, Switzerland.

[6] World Health Organization 2014, posting date Avian influenza in humans. WHO, Geneva, Switzerland.

[7] Zhu Y, Qi X, Cui L, Zhou M, Wang H. 2013. Human co-infection with novel avian influenza A H7N9 and influenza A H3N2 viruses in Jiangsu province, China. Lancet 381:2134. 10.1016/S0140-6736(13)61135-6. - DOI - PubMed

[8] Zhu Y, Qi X, Cui L, Zhou M, Wang H. 2013. Human co-infection with novel avian influenza A H7N9 and influenza A H3N2 viruses in Jiangsu province, China. Lancet 381:2134. 10.1016/S0140-6736(13)61135-6. - DOI - PubMed

[9] Li J, Kou Y, Yu X, Sun Y, Zhou Y, Pu X, Jin T, Pan J, Gao GF. 2014. Human co-infection with avian and seasonal influenza viruses, china. Emerg. Infect. Dis. 20:1953–1955. 10.3201/eid2011.140897. - DOI - PMC - PubMed

[10] Li J, Kou Y, Yu X, Sun Y, Zhou Y, Pu X, Jin T, Pan J, Gao GF. 2014. Human co-infection with avian and seasonal influenza viruses, china. Emerg. Infect. Dis. 20:1953–1955. 10.3201/eid2011.140897. - DOI - PMC - PubMed

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Influenza gain-of-function experiments: their role in vaccine virus recommendation and pandemic preparedness

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Influenza gain-of-function experiments: their role in vaccine virus recommendation and pandemic preparedness

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