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J Infect Dis. 2016 Dec 15;214(12):1937-1946. Epub 2016 Oct 12.

Cross-immunity Against Avian Influenza A(H7N9) Virus in the Healthy Population Is Affected by Antigenicity-Dependent Substitutions.

Liu WJ1,2, Tan S3,4, Zhao M3,4, Quan C1, Bi Y3, Wu Y3, Zhang S3, Zhang H2, Xiao H5, Qi J3, Yan J3, Liu W3, Yu H6, Shu Y1, Wu G1, Gao GF1,3,7,4,2.

Author information

Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention.
College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology.
University of Chinese Academy of Sciences, Beijing.
Laboratory of Protein Engineering and Vaccine, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
Division of Infectious Disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention.
Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences.



 The emergence of infections by the novel avian influenza A(H7N9) virus has posed a threat to human health. Cross-immunity between A(H7N9) and other heterosubtypic influenza viruses affected by antigenicity-dependent substitutions needs to be investigated.


 We investigated the cellular and humoral immune responses against A(H7N9) and 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09), by serological and T-cell-specific assays, in a healthy population. The molecular bases of the cellular and humoral antigenic variability of A(H7N9) were illuminated by structural determination.


 We not only found that antibodies against A(H7N9) were lacking in the studied population, but also revealed that both CD4+ and CD8+ T cells that cross-reacted with A(H7N9) were at significantly lower levels than those against the A(H1N1)pdm09 peptides with substitutions. Moreover, individual peptides for A(H7N9) with low cross-reactivity were identified. Structural determination indicated that substitutions within these peptides influence the antigenic variability of A(H7N9) through both major histocompatibility complex (MHC) binding and T-cell receptor docking.


 The impact of antigenicity-dependent substitutions on cross-reactivity of T-cell immunity against the novel influenza virus A(H7N9) in the healthy population benefits the understanding of immune evasion of influenza viruses and provides a useful reference for universal vaccine development.


T-cell response; antigenic variation; avian influenza A(H7N9) virus; cross-reactivity; structure

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