Science China Life Sciences

, Volume 61, Issue 12, pp 1465–1473 | Cite as

Vaccination of poultry successfully eliminated human infection with H7N9 virus in China

  • Xianying Zeng
  • Guobin Tian
  • Jianzhong Shi
  • Guohua Deng
  • Chengjun Li
  • Hualan Chen
Review From CAS & CAE Members


The H7N9 viruses that emerged in China in 2013 were nonpathogenic in chickens but mutated to a highly pathogenic form in early 2017 and caused severe disease outbreaks in chickens. The H7N9 influenza viruses have caused five waves of human infection, with almost half of the total number of human cases (766 of 1,567) being reported in the fifth wave, raising concerns that even more human infections could occur in the sixth wave. In September 2017, an H5/H7 bivalent inactivated vaccine for chickens was introduced, and the H7N9 virus isolation rate in poultry dropped by 93.3% after vaccination. More importantly, only three H7N9 human cases were reported between October 1, 2017 and September 30, 2018, indicating that vaccination of poultry successfully eliminated human infection with H7N9 virus. These facts emphasize that active control of animal disease is extremely important for zoonosis control and human health protection.


H7N9 influenza virus evolution vaccination human infection elimination 



This work was supported by the National Key R&D Program of China (2016YFD0500201, 2016YFD0500203), the National Natural Science Foundation of China (31521005), and the China Agriculture Research System (CARS-41-G12).


  1. Alexander, D., and Brown, I. (2009). History of highly pathogenic avian influenza. Rev Sci Tech OIE 28, 19–38.CrossRefGoogle Scholar
  2. Belser, J., Gustin, K., Pearce, M., Maines, T., Zeng, H., Pappas, C., Sun, X., Carney, P., Villanueva, J., Stevens, J., et al. (2013). Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice. Nature 501, 556–559.CrossRefGoogle Scholar
  3. Chen, B., Zhang, Z., and Chen, W. (1994). Isolation and preliminary serological characterization of type A influenza viruses from chickens. Chin J Vet Med 22, 3–5.Google Scholar
  4. Chen, H. (2009a). Avian influenza vaccination: the experience in China. Rev Sci Tech OIE 28, 267–274.CrossRefGoogle Scholar
  5. Chen, H. (2009b). H5N1 avian influenza in China. Sci China Ser C-Life Sci 52, 419–427.CrossRefGoogle Scholar
  6. Chen, H., Yuan, H., Gao, R., Zhang, J., Wang, D., Xiong, Y., Fan, G., Yang, F., Li, X., Zhou, J., et al. (2014). Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study. Lancet 383, 714–721.CrossRefGoogle Scholar
  7. Chen, L., Blixt, O., Stevens, J., Lipatov, A., Davis, C., Collins, B., Cox, N., Paulson, J., and Donis, R. (2012). In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity. Virology 422, 105–113.CrossRefGoogle Scholar
  8. Deng, G., Shi, J., Wang, J., Kong, H., Cui, P., Zhang, F., Tan, D., Suzuki, Y., Liu, L., Jiang, Y., et al. (2015). Genetics, receptor binding, and virulence in mice of H10N8 influenza viruses isolated from ducks and chickens in live poultry markets in China. J Virol 89, 6506–6510.CrossRefGoogle Scholar
  9. Feng, X., Wang, Z., Shi, J., Deng, G., Kong, H., Tao, S., Li, C., Liu, L., Guan, Y., and Chen, H. (2016). Glycine at position 622 in PB1 contributes to the virulence of H5N1 avian influenza virus in mice. J Virol 90, 1872–1879.CrossRefGoogle Scholar
  10. Gabriel, G., Dauber, B., Wolff, T., Planz, O., Klenk, H.D., and Stech, J. (2005). The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc Natl Acad Sci USA 102, 18590–18595.CrossRefGoogle Scholar
  11. Gao, R., Cao, B., Hu, Y., Feng, Z., Wang, D., Hu, W., Chen, J., Jie, Z., Qiu, H., Xu, K., et al. (2013). Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 368, 1888–1897.CrossRefGoogle Scholar
  12. Gao, Y., Zhang, Y., Shinya, K., Deng, G., Jiang, Y., Li, Z., Guan, Y., Tian, G., Li, Y., Shi, J., et al. (2009). Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLoS Pathog 5, e1000709.CrossRefGoogle Scholar
  13. Ge, J., Deng, G., Wen, Z., Tian, G., Wang, Y., Shi, J., Wang, X., Li, Y., Hu, S., Jiang, Y., et al. (2007). Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses. J Virology 81, 150–158.CrossRefGoogle Scholar
  14. Hatta, M., Gao, P., Halfmann, P., and Kawaoka, Y. (2001). Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293, 1840–1842.CrossRefGoogle Scholar
  15. Hatta, M., Hatta, Y., Kim, J.H., Watanabe, S., Shinya, K., Nguyen, T., Lien, P.S., Le, Q.M., and Kawaoka, Y. (2007). Growth of H5N1 influenza a viruses in the upper respiratory tracts of mice. PLoS Pathog 3, e133–1379.CrossRefGoogle Scholar
  16. Herfst, S., Schrauwen, E., Linster, M., Chutinimitkul, S., de Wit, E., Munster, V., Sorrell, E., Bestebroer, T., Burke, D., Smith, D., et al. (2012). Airborne transmission of influenza A/H5N1 virus between ferrets. Science 336, 1534–1541.CrossRefGoogle Scholar
  17. Homme, P., and Easterday, B. (1970). Avian influenza virus infections. I. Characteristics of influenza A-turkey-Wisconsin-1966 virus. Avian Dis 14, 66–74.CrossRefGoogle Scholar
  18. Imai, M., Watanabe, T., Hatta, M., Das, S.C., Ozawa, M., Shinya, K., Zhong, G., Hanson, A., Katsura, H., Watanabe, S., et al. (2012). Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486, 420–428.CrossRefGoogle Scholar
  19. Jiang, Y., Yu, K., Zhang, H., Zhang, P., Li, C., Tian, G., Li, Y., Wang, X., Ge, J., Bu, Z., et al. (2007). Enhanced protective efficacy of H5 subtype avian influenza DNA vaccine with codon optimized HA gene in a pCAGGS plasmid vector. Antiviral Res 75, 234–241.CrossRefGoogle Scholar
  20. Jiao, P., Tian, G., Li, Y., Deng, G., Jiang, Y., Liu, C., Liu, W., Bu, Z., Kawaoka, Y., and Chen, H. (2008). A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. J Virology 82, 1146–1154.CrossRefGoogle Scholar
  21. Kilbourne, E.D. (2006). Influenza pandemics of the 20th century. Emerg Infect Dis 12, 9–14.CrossRefGoogle Scholar
  22. Kong, H., Zhang, Q., Gu, C., Shi, J., Deng, G., Ma, S., Liu, J., Chen, P., Guan, Y., Jiang, Y., et al. (2015). A live attenuated vaccine prevents replication and transmission of H7N9 virus in mammals. Sci Rep 5, 11233.CrossRefGoogle Scholar
  23. Li, C., Yu, K., Tian, G., Yu, D., Liu, L., Jing, B., Ping, J., and Chen, H. (2005a). Evolution of H9N2 influenza viruses from domestic poultry in Mainland China. Virology 340, 70–83.CrossRefGoogle Scholar
  24. Li, C., Bu, Z., and Chen, H. (2014a). Avian influenza vaccines against H5N1 ‘bird flu’. Trends Biotech 32, 147–156.CrossRefGoogle Scholar
  25. Li, C., and Chen, H. (2014). Enhancement of influenza virus transmission by gene reassortment. Curr Top Microbiol 385, 185–204.Google Scholar
  26. Li, X., Shi, J., Guo, J., Deng, G., Zhang, Q., Wang, J., He, X., Wang, K., Chen, J., Li, Y., et al. (2014b). Genetics, receptor binding property, and transmissibility in mammals of naturally isolated H9N2 Avian Influenza viruses. PLoS Pathog 10, e1004508.CrossRefGoogle Scholar
  27. Li, Y., Shi, J., Zhong, G., Deng, G., Tian, G., Ge, J., Zeng, X., Song, J., Zhao, D., Liu, L., et al. (2010). Continued evolution of H5N1 influenza viruses in wild birds, domestic poultry, and humans in China from 2004 to 2009. J Virology 84, 8389–8397.CrossRefGoogle Scholar
  28. Li, Z., Chen, H., Jiao, P., Deng, G., Tian, G., Li, Y., Hoffmann, E., Webster, R.G., Matsuoka, Y., and Yu, K. (2005b). Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J Virology 79, 12058–12064.CrossRefGoogle Scholar
  29. Liu, J., Chen, P., Jiang, Y., Wu, L., Zeng, X., Tian, G., Ge, J., Kawaoka, Y., Bu, Z., and Chen, H. (2011). A duck enteritis virus-vectored bivalent live vaccine provides fast and complete protection against H5N1 avian influenza virus infection in ducks. J Virology 85, 10989–10998.CrossRefGoogle Scholar
  30. Lowen, A., Mubareka, S., Tumpey, T., García-Sastre, A., and Palese, P. (2006). The guinea pig as a transmission model for human influenza viruses. Proc Natl Acad Sci USA 103, 9988–9992.CrossRefGoogle Scholar
  31. Lu, X., Tumpey, T., Morken, T., Zaki, S., Cox, N., and Katz, J. (1999). A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. J Virol 73, 5903–5911.Google Scholar
  32. MARA of China. (2018). Bulletin No. 30. Scholar
  33. Neumann, G., and Kawaoka, Y. (2006). Host range restriction and pathogenicity in the context of influenza pandemic. Emerg Infect Dis 12, 881–886.CrossRefGoogle Scholar
  34. Pantin-Jackwood, M., Miller, P., Spackman, E., Swayne, D., Susta, L., Costa-Hurtado, M., and Suarez, D. (2014). Role of poultry in the spread of novel H7N9 influenza virus in China. J Virology 88, 5381–5390.CrossRefGoogle Scholar
  35. Qi, W., Jia, W., Liu, D., Li, J., Bi, Y., Xie, S., Li, B., Hu, T., Du, Y., Xing, L., et al. (2018). Emergence and adaptation of a novel highly pathogenic H7N9 influenza virus in birds and humans from a 2013 human-infecting low-pathogenic ancestor. J Virol 92.Google Scholar
  36. Richard, M., Schrauwen, E., de Graaf, M., Bestebroer, T., Spronken, M., van Boheemen, S., de Meulder, D., Lexmond, P., Linster, M., Herfst, S., et al. (2013). Limited airborne transmission of H7N9 influenza A virus between ferrets. Nature 501, 560–563.CrossRefGoogle Scholar
  37. Rogers, G., and Paulson, J. (1983). Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 127, 361–373.CrossRefGoogle Scholar
  38. Shi, J., Deng, G., Kong, H., Gu, C., Ma, S., Yin, X., Zeng, X., Cui, P., Chen, Y., Yang, H., et al. (2017). H7N9 virulent mutants detected in chickens in China pose an increased threat to humans. Cell Res 27, 1409–1421.CrossRefGoogle Scholar
  39. Shi, J., Deng, G., Ma, S., Zeng, X., Yin, X., Li, M., Zhang, B., Cui, P., Chen, Y., Yang, H., et al. (2018). Rapid evolution of H7N9 highly pathogenic viruses that emerged in China in 2017. Cell Host Microbe 24, 558–568.e7.CrossRefGoogle Scholar
  40. Shi, J., Deng, G., Liu, P., Zhou, J., Guan, L., Li, W., Li, X., Guo, J., Wang, G., Fan, J., et al. (2013). Isolation and characterization of H7N9 viruses from live poultry markets — Implication of the source of current H7N9 infection in humans. Chin Sci Bull 58, 1857–1863.CrossRefGoogle Scholar
  41. Shi, J., Deng, G., Zeng, X., Kong, H., Wang, X., Lu, K., Wang, X., Mu, G., Xu, X., Cui, P., et al. (2014). Novel influenza A(H7N2) virus in chickens, Jilin Province, China, 2014. Emerg Infect Dis 20, 1719–1722.CrossRefGoogle Scholar
  42. Steel, J., Lowen, A.C., Mubareka, S., and Palese, P. (2009). Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog 5, e1000252.CrossRefGoogle Scholar
  43. Subbarao, K., London, W., and Murphy, B. (1993). A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol 67, 1761–1764.Google Scholar
  44. Swayne, D. (2012). Impact of vaccines and vaccination on global control of avian influenza. Avian Dis 56, 818–828.CrossRefGoogle Scholar
  45. Tian, G., Zhang, S., Li, Y., Bu, Z., Liu, P., Zhou, J., Li, C., Shi, J., Yu, K., and Chen, H. (2005). Protective efficacy in chickens, geese and ducks of an H5N1-inactivated vaccine developed by reverse genetics. Virology 341, 153–162.CrossRefGoogle Scholar
  46. Vasin, A., Temkina, O., Egorov, V., Klotchenko, S., Plotnikova, M., and Kiselev, O. (2014). Molecular mechanisms enhancing the proteome of influenza A viruses: an overview of recently discovered proteins. Virus Res 185, 53–63.CrossRefGoogle Scholar
  47. Wang, Z., Yang, H., Chen, Y., Tao, S., Liu, L., Kong, H., Ma, S., Meng, F., Suzuki, Y., Qiao, C., et al. (2017). A single-amino-acid substitution at position 225 in hemagglutinin alters the transmissibility of eurasian avian-Like H1N1 swine influenza virus in guinea pigs. J Virol 91.Google Scholar
  48. Watanabe, T., Kiso, M., Fukuyama, S., Nakajima, N., Imai, M., Yamada, S., Murakami, S., Yamayoshi, S., Iwatsuki-Horimoto, K., Sakoda, Y., et al. (2013). Characterization of H7N9 influenza A viruses isolated from humans. Nature 501, 551–555.CrossRefGoogle Scholar
  49. World Health Organization. (2018). Influenza at the human-animal interface. Scholar
  50. World Organisation for Animal Health. (2017). Scholar
  51. Xiong, X., Martin, S., Haire, L., Wharton, S., Daniels, R., Bennett, M., McCauley, J., Collins, P., Walker, P., Skehel, J., et al. (2013). Receptor binding by an H7N9 influenza virus from humans. Nature 499, 496–499.CrossRefGoogle Scholar
  52. Yang, H., Chen, Y., Qiao, C., He, X., Zhou, H., Sun, Y., Yin, H., Meng, S., Liu, L., Zhang, Q., et al. (2016). Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses. Proc Natl Acad Sci USA 113, 392–397.CrossRefGoogle Scholar
  53. Yang, L., Zhu, W., Li, X., Chen, M., Wu, J., Yu, P., Qi, S., Huang, Y., Shi, W., Dong, J., et al. (2017). Genesis and spread of newly emerged highly pathogenic H7N9 avian viruses in mainland China. J Virol 91.Google Scholar
  54. Yang, W., Yin, X., Guan, L., Li, M., Ma, S., Shi, J., Deng, G., Suzuki, Y., and Chen, H. (2018). A live attenuated vaccine prevents replication and transmission of H7N9 highly pathogenic influenza viruses in mammals. Emerg Microbes Infect 7, 153.CrossRefGoogle Scholar
  55. Zeng, X., Chen, P., Liu, L., Deng, G., Li, Y., Shi, J., Kong, H., Feng, H., Bai, J., Li, X., et al. (2016). Protective efficacy of an H5N1 inactivated vaccine against challenge with lethal H5N1, H5N2, H5N6, and H5N8 influenza viruses in chickens. Avian Dis 60, 253–255.CrossRefGoogle Scholar
  56. Zhang, Q., Shi, J., Deng, G., Guo, J., Zeng, X., He, X., Kong, H., Gu, C., Li, X., Liu, J., et al. (2013a). H7N9 influenza viruses are transmissible in ferrets by respiratory droplet. Science 341, 410–414.CrossRefGoogle Scholar
  57. Zhang, Y., Zhang, Q., Gao, Y., He, X., Kong, H., Jiang, Y., Guan, Y., Xia, X., Shu, Y., Kawaoka, Y., et al. (2012). Key molecular factors in hemagglutinin and PB2 contribute to efficient transmission of the 2009 H1N1 pandemic influenza virus. J Virol 86, 9666–9674.CrossRefGoogle Scholar
  58. Zhang, Y., Zhang, Q., Kong, H., Jiang, Y., Gao, Y., Deng, G., Shi, J., Tian, G., Liu, L., Liu, J., et al. (2013b). H5N1 hybrid viruses bearing 2009/H1N1 virus genes transmit in guinea pigs by respiratory droplet. Science 340, 1459–1463.CrossRefGoogle Scholar
  59. Zhou, J., Wang, D., Gao, R., Zhao, B., Song, J., Qi, X., Zhang, Y., Shi, Y., Yang, L., Zhu, W., et al. (2013). Biological features of novel avian influenza A (H7N9) virus. Nature 499, 500–503.CrossRefGoogle Scholar
  60. Zhu, H., Wang, D., Kelvin, D.J., Li, L., Zheng, Z., Yoon, S.W., Wong, S.S., Farooqui, A., Wang, J., Banner, D., et al. (2013). Infectivity, transmission, and pathology of human-isolated H7N9 influenza virus in ferrets and pigs. Science 341, 183–186.CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Xianying Zeng
    • 1
  • Guobin Tian
    • 1
  • Jianzhong Shi
    • 1
  • Guohua Deng
    • 1
  • Chengjun Li
    • 1
  • Hualan Chen
    • 1
  1. 1.State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbinChina

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